36 results on '"Eugenia Corrales-Aguilar"'
Search Results
2. Susceptibility of Well-Differentiated Airway Epithelial Cell Cultures from Domestic and Wild Animals to Severe Acute Respiratory Syndrome Coronavirus 2
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Mitra Gultom, Matthias Licheri, Laura Laloli, Manon Wider, Marina Strässle, Philip V’kovski, Silvio Steiner, Annika Kratzel, Tran Thi Nhu Thao, Lukas Probst, Hanspeter Stalder, Jasmine Portmann, Melle Holwerda, Nadine Ebert, Nadine Stokar-Regenscheit, Corinne Gurtner, Patrik Zanolari, Horst Posthaus, Simone Schuller, Amanda Vicente-Santos, Andres Moreira-Soto, Eugenia Corrales-Aguilar, Nicolas Ruggli, Gergely Tekes, Veronika von Messling, Bevan Sawatsky, Volker Thiel, and Ronald Dijkman
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animal experimentation ethics ,coronavirus disease ,disease reservoirs ,epidemics ,epithelial cells ,outbreaks ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, and the number of worldwide cases continues to rise. The zoonotic origins of SARS-CoV-2 and its intermediate and potential spillback host reservoirs, besides humans, remain largely unknown. Because of ethical and experimental constraints and more important, to reduce and refine animal experimentation, we used our repository of well-differentiated airway epithelial cell (AEC) cultures from various domesticated and wildlife animal species to assess their susceptibility to SARS-CoV-2. We observed that SARS-CoV-2 replicated efficiently only in monkey and cat AEC culture models. Whole-genome sequencing of progeny viruses revealed no obvious signs of nucleotide transitions required for SARS-CoV-2 to productively infect monkey and cat AEC cultures. Our findings, together with previous reports of human-to-animal spillover events, warrant close surveillance to determine the potential role of cats, monkeys, and closely related species as spillback reservoirs for SARS-CoV-2.
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- 2021
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3. Development and characterization of two equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19
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Guillermo León, María Herrera, Mariángela Vargas, Mauricio Arguedas, Andrés Sánchez, Álvaro Segura, Aarón Gómez, Gabriela Solano, Eugenia Corrales-Aguilar, Kenneth Risner, Aarthi Narayanan, Charles Bailey, Mauren Villalta, Andrés Hernández, Adriana Sánchez, Daniel Cordero, Daniela Solano, Gina Durán, Eduardo Segura, Maykel Cerdas, Deibid Umaña, Edwin Moscoso, Ricardo Estrada, Jairo Gutiérrez, Marcos Méndez, Ana Cecilia Castillo, Laura Sánchez, Ronald Sánchez, José María Gutiérrez, Cecilia Díaz, and Alberto Alape
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Medicine ,Science - Abstract
Abstract In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited high in vitro neutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.
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- 2021
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4. Passive epidemiological surveillance in wildlife in Costa Rica identifies pathogens of zoonotic and conservation importance
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Fernando Aguilar-Vargas, Tamara Solorzano-Scott, Mario Baldi, Elías Barquero-Calvo, Ana Jiménez-Rocha, Carlos Jiménez, Marta Piche-Ovares, Gaby Dolz, Bernal León, Eugenia Corrales-Aguilar, Mario Santoro, and Alejandro Alfaro-Alarcón
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Medicine ,Science - Abstract
Epidemiological surveillance systems for pathogens in wild species have been proposed as a preventive measure for epidemic events. These systems can minimize the detrimental effects of an outbreak, but most importantly, passive surveillance systems are the best adapted to countries with limited resources. Therefore, this research aimed to evaluate the technical and infrastructural feasibility of establishing this type of scheme in Costa Rica by implementing a pilot program targeting the detection of pathogens of zoonotic and conservation importance in wildlife. Between 2018 and 2020, 85 carcasses of free-ranging vertebrates were admitted for post-mortem and microbiology analysis. However, we encountered obstacles mainly related to the initial identification of cases and limited local logistics capacity. Nevertheless, this epidemiological surveillance scheme allowed us to estimate the general state of health of the country’s wildlife by establishing the causes of death according to pathological findings. For instance, 60% (51/85) of the deaths were not directly associated with an infectious agent. Though in 37.6% (32/85) of these cases an infectious agent associated or not with disease was detected. In 27.1% (23/85) of the cases, death was directly related to infectious agents. Furthermore, 12.9% (11/85), the cause of death was not determined. Likewise, this wildlife health monitoring program allowed the detection of relevant pathogens such as Canine Distemper Virus, Klebsiella pneumoniae, Angiostrongylus spp., Baylisascaris spp., among others. Our research demonstrated that this passive surveillance scheme is cost-effective and feasible in countries with limited resources. This passive surveillance can be adapted to the infrastructure dedicated to monitoring diseases in productive animals according to the scope and objectives of monitoring wildlife specific to each region. The information generated from the experience of the initial establishment of a WHMP is critical to meeting the challenges involved in developing this type of scheme in regions with limited resources and established as hotspots for emerging infectious diseases.
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- 2022
5. Serosurvey in Two Dengue Hyperendemic Areas of Costa Rica Evidence Active Circulation of WNV and SLEV in Peri-Domestic and Domestic Animals and in Humans
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Marta Piche-Ovares, Mario Romero-Vega, Diana Vargas-González, Daniel Felipe Barrantes Murillo, Claudio Soto-Garita, Jennifer Francisco-Llamas, Alejandro Alfaro-Alarcón, Carlos Jiménez, and Eugenia Corrales-Aguilar
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flavivirus ,Costa Rica ,WNV ,SLEV ,seroepidemiology ,Medicine - Abstract
Costa Rica harbors several flaviviruses, including Dengue (DENV), Zika (ZIKV), West Nile virus (WNV), and Saint Louis encephalitis virus (SLEV). While DENV and ZIKV are hyperendemic, previous research indicates restricted circulation of SLEV and WNV in animals. SLEV and WNV seroprevalence and high transmission areas have not yet been measured. To determine the extents of putative WNV and SLEV circulation, we sampled peri-domestic and domestic animals, humans, and mosquitoes in rural households located in two DENV and ZIKV hyperendemic regions during the rainy and dry seasons of 2017–2018 and conducted plaque reduction neutralization test assay for serology (PRNT) and RT-PCR for virus detection. In Cuajiniquil, serological evidence of WNV and SLEV was found in equines, humans, chickens, and wild birds. Additionally, five seroconversion events were recorded for WNV (2 equines), SLEV (1 human), and DENV-1 (2 humans). In Talamanca, WNV was not found, but serological evidence of SLEV circulation was recorded in equines, humans, and wild birds. Even though no active viral infection was detected, the seroconversion events recorded here indicate recent circulation of SLEV and WNV in these two regions. This study thus provides clear-cut evidence for WNV and SLEV presence in these areas, and therefore, they should be considered in arboviruses differential diagnostics and future infection prevention campaigns.
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- 2022
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6. Bats and Viruses: Current Research and Future Trends
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Eugenia Corrales-Aguilar, Martin Schwemmle, and David Hewitt
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zooonoses ,virology ,mammals ,bats ,viruses ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Published
- 2021
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7. Nuevas perspectivas sobre la patogénesis del dengue New Perspectives on Dengue Pathogenesis
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Eugenia Corrales-Aguilar and Laya Hun-Opfer
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dengue ,virus ,patogénesis ,dengue grave ,pathogenesis ,severe dengue ,Medicine - Abstract
El dengue es una enfermedad viral de gran importancia en la salud pública. Sin embargo, los mecanismos de patogénesis por el virus del dengue (DENV) no están bien definidos, ya que no existen modelos animales apropiados para estudiar el curso de la enfermedad. Únicamente se cuenta con datos de pacientes, los cuales son muy diversos y no permiten aún entender bien los fenómenos patológicos que ocurren en el transcurso de la infección. No obstante, varios factores parecen estar relacionados con la patogénesis de DENV: i) factores virales, tales como la virulencia y la transmisibilidad del virus, y ii) factores del hospedero, tales como la respuesta inmune, la naturaleza de su estado inmunológico y sus características genéticas. En la presente revisión se exponen los factores que desempeñan un papel fundamental en la patogénesis del dengue, para así comprender mejor el curso de la enfermedad y permitir un más adecuado abordaje terapéutico de los pacientes. En vista de que la clasificación utilizada para definir los factores de riesgo durante una infección por dengue, ya no es congruente con estudios clínicos realizados, se plantea la nueva clasificación de la enfermedad dictada por la Organización Mundial de la Salud (OMS).Dengue viral infections represent a major concern for public health. Yet, the mechanisms of dengue virus (DENV) pathogenesis are not understood very well yet, since there are no suitable animal models for studying the course of disease. The only source of knowledge is limited to clinical studies involving patients, which vary a lot and do not allow for the accurate understanding of the pathological events that occur during viral infection. Nevertheless, several factors seem to be related to DENV pathogenesis: i) viral factors, such as virulence and virus transmissibility and ii) host determinants like the immune response, immune status and genetic characteristics. In this review we describe the factors that play an important role in dengue pathogenesis in order to have a better understanding of the disease and to allow for a more suitable therapeutic management of patients. Since the current disease classification used for determining risk factors during the course of a dengue infection is no longer congruent with the clinical studies performed, the use of the new dengue disease classification dictated by the World Health Organization (WHO) is suggested.
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- 2012
8. Susceptibility of Well-Differentiated Airway Epithelial Cell Cultures from Domestic and Wild Animals to Severe Acute Respiratory Syndrome Coronavirus 2
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Philip V'kovski, Tran Thi Nhu Thao, Andres Moreira-Soto, Bevan Sawatsky, Nicolas Ruggli, Patrik Zanolari, Simone Schuller, Manon Wider, Volker Thiel, Eugenia Corrales-Aguilar, Annika Kratzel, Horst Posthaus, Melle Holwerda, Corinne Gurtner, Nadine Stokar-Regenscheit, Amanda Vicente-Santos, Lukas Probst, Hanspeter Stalder, Nadine Ebert, Gergely Tekes, Matthias Licheri, Veronika von Messling, Laura Laloli, Jasmine Portmann, Ronald Dijkman, Marina Strässle, Silvio Steiner, and Mitra L. Gultom
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Microbiology (medical) ,Disease reservoir ,Epidemiology ,Susceptibility of Well-Differentiated Airway Epithelial Cell Cultures from Domestic and Wild Animals to Severe Acute Respiratory Syndrome Coronavirus 2 ,viruses ,Respiratory System ,severe acute respiratory syndrome 2 ,Animals, Wild ,Infectious and parasitic diseases ,RC109-216 ,Biology ,epidemics ,03 medical and health sciences ,respiratory infections ,medicine ,Animals ,Humans ,Respiratory system ,Animal testing ,skin and connective tissue diseases ,030304 developmental biology ,Original Research ,Whole genome sequencing ,0303 health sciences ,whole genome sequencing ,CATS ,030306 microbiology ,SARS-CoV-2 ,Research ,fungi ,Outbreak ,COVID-19 ,disease reservoirs ,respiratory system ,Virology ,Epithelium ,epithelial cells ,3. Good health ,zoonoses ,respiratory tract diseases ,Infectious Diseases ,medicine.anatomical_structure ,coronavirus disease ,outbreaks ,animal experimentation ethics ,Medicine ,Airway - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, and the number of worldwide cases continues to rise. The zoonotic origins of SARS-CoV-2 and its intermediate and potential spillback host reservoirs, besides humans, remain largely unknown. Because of ethical and experimental constraints and more important, to reduce and refine animal experimentation, we used our repository of well-differentiated airway epithelial cell (AEC) cultures from various domesticated and wildlife animal species to assess their susceptibility to SARS-CoV-2. We observed that SARS-CoV-2 replicated efficiently only in monkey and cat AEC culture models. Whole-genome sequencing of progeny viruses revealed no obvious signs of nucleotide transitions required for SARS-CoV-2 to productively infect monkey and cat AEC cultures. Our findings, together with previous reports of human-to-animal spillover events, warrant close surveillance to determine the potential role of cats, monkeys, and closely related species as spillback reservoirs for SARS-CoV-2.
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- 2021
9. Serological Positivity against Selected Flavivirus and Alphavirus in Free-ranging Bats and Birds from Costa Rica Evidence Exposure to Arboviruses Seldom Reported Locally in Humans
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Luis Mario Romero, Jose Carlos Gamboa Solano, Marta Piche-Ovares, Claudio Soto-Garita, Eugenia Corrales-Aguilar, Daniel Felipe Barrantes Murillo, and Alejandro Alfaro-Alarcón
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biology ,Free ranging ,viruses ,Wildlife ,virus diseases ,Alphavirus ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,biology.organism_classification ,Arbovirus ,Virology ,Serology ,Flavivirus ,medicine - Abstract
Arboviruses have two ecological transmission cycles, sylvatic and urban. For some, the sylvatic cycle has not been thoroughly described in America. To study the role of wildlife in a putative sylvatic cycle, we sampled free-ranging bats and birds in two arbovirus endemic locations and analyzed them using molecular, serological, and histological methods. No current infection was detected, and no significant arbovirus-associated histological changes were observed. Neutralizing antibodies were detected against selected arboviruses. In bats, positivity in 34.95% for DENV-1, 16.26% for DENV-2, 5.69% for DENV-3, 4.87% for DENV-4, 2.43% for WNV, 4.87% for SLEV, 0,81% for YFV, 7.31% for EEEV, and 0.81% for VEEV was found. Antibodies against ZIKV were not detected. In birds, PRNT results were positive against WNV in 0.80%, SLEV in 5.64%, EEEV in 8.4%, and VEEV in 5.63%. An additional retrospective PRNT analysis was performed using bat samples from three additional DENV endemic sites resulting in a 3.27% prevalence for WNV and 1.63% for SLEV. Interestingly one sample resulted unequivocally WNV positive confirmed by serum titration. These results suggest that free-ranging bats and birds are exposed to not currently reported hyperendemic-human infecting Flavivirus and Alphavirus, however, their role as reservoirs or hosts is still undetermined.
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- 2021
10. Serosurvey in two rural areas evidences recent and previously undetected WNV and SLEV circulation in Costa Rica
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Carlos Jiménez, Eugenia Corrales-Aguilar, Diana Vargas-González, Marta Piche-Ovares, Mario Romero-Vega, Daniel Barrantes-Murillo, Jennifer Francisco-Llamas, Claudio Soto-Garita, and Alejandro Alfaro-Alarcón
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DENGUE ,Transmission (medicine) ,viruses ,MOSQUITOES ,virus diseases ,MOSQUITOS ,INFECTIOUS DISEASES ,Biology ,medicine.disease ,Virology ,Arbovirus ,Serology ,Dengue fever ,ENFERMEDADES INFECCIOSAS ,Saint Louis encephalitis ,medicine ,Seroprevalence ,VIRUS ,Seroconversion ,Encephalitis - Abstract
West Nile virus (WNV) and Saint Louis encephalitis virus (SLEV) share similar virus transmission cycles that involve birds as amplifiers and mosquitoes as vectors. Mammals, including humans, are dead-end-hosts that may be asymptomatic or develop more severe symptoms. Costa Rica is a hyperendemic country for several flaviviruses such as Dengue (DENV) and Zika (ZIKV) and previous research showed limited and restricted SLEV and WNV circulation in horses, sloths, and monkeys. Nevertheless, actual seroprevalence and high transmission areas are not yet identified. To determine putative WNV and SLEV circulation, we sampled peri domestic and domestic animals, humans, wild birds, and mosquitoes in rural households located in two DENV and ZIKV hyperendemic regions during the rainy and dry seasons of 2017-2018 and conducted PRNT assays for serology and RT PCR for virus detection. At Cuajiniquil, serological evidence of WNV and SLEV was found in equines, humans, chickens, and wild birds. Also, 5 seroconversion events were recorded for WNV (2 equine), SLEV (1 human), and DENV-1 (2 humans). At Talamanca, a lack of WNV circulation was found, but evidence of SLEV circulation was recorded in equines, humans, and wild birds. No evidence of active viral infection was found in any mosquitoes or wild bird samples. This seroconversion evidence supports the active and recent circulation of SLEV and WNV in these two regions. This study provides clear-cut evidence of WNV and SLEV circulation and should be considered by the health and epidemiology authorities for future prevention and differential diagnostics. El virus del Nilo Occidental (VNO) y el virus de la encefalitis de San Luis (SLEV) comparten ciclos de transmisión del virus similares que implican a las aves como amplificadores y a los mosquitos como vectores. Los mamíferos, incluidos los humanos, son huéspedes muertos que pueden ser asintomáticos o desarrollar síntomas más graves. Costa Rica es un país hiperendémico para varios flavivirus como el dengue (DENV) y el zika (ZIKV) y las investigaciones anteriores mostraron una circulación limitada y restringida del SLEV y el WNV en caballos, perezosos y monos. Sin embargo, aún no se ha identificado la seroprevalencia real ni las zonas de alta transmisión. Para determinar la circulación putativa del WNV y el SLEV, tomamos muestras de animales peri domésticos y domésticos, humanos, aves silvestres y mosquitos en hogares rurales ubicados en dos regiones hiperendémicas de DENV y ZIKV durante las estaciones lluviosas y secas de 2017-2018 y realizamos ensayos de PRNT para la serología y RT PCR para la detección del virus. En Cuajiniquil, se encontraron evidencias serológicas de VNO y SLEV en equinos, humanos, pollos y aves silvestres. Además, se registraron 5 eventos de seroconversión para el VNO (2 equinos), el SLEV (1 humano) y el DENV-1 (2 humanos). En Talamanca, no se encontró circulación del VNO, pero se registraron evidencias de circulación del SLEV en equinos, humanos y aves silvestres. No se encontró evidencia de infección viral activa en ningún mosquito ni en muestras de aves silvestres. Estas pruebas de seroconversión apoyan la circulación activa y reciente del SLEV y el VNO en estas dos regiones. Este estudio proporciona pruebas claras de la circulación del VNO y el SLEV y debería ser considerado por las autoridades sanitarias y epidemiológicas para la prevención y el diagnóstico diferencial en el futuro. Universidad Nacional, Costa Rica Escuela de Medicina Veterinaria
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- 2021
11. High Efficacy of Therapeutic Equine Hyperimmune Antibodies Against SARS-CoV-2 Variants of Concern
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Chantal Reusken, Román Macaya, Alfredo Sanabria, Chistian Drosten, Ann Echeverri, Mariángela Vargas, Álvaro Segura, María Herrera, Jose Arturo Molina-Mora, Alberto Alape-Girón, José María Gutiérrez, Hebleen Brenes, Javier Mora, Arne Khüne, Mauricio Arguedas, Willem Buján, Mauren Villalta, Eduardo Segura, Andrés Sánchez, Guillermo León, Laura Sánchez, Claudio Soto, Daniela Solano, Aarón Gómez, Jennifer Lynn Stynoski, Eugenia Corrales-Aguilar, Andrés Hernández, Andres Moreira-Soto, Jan Felix Drexler, Marietta Flores-Díaz, and Cecilia Díaz
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2019-20 coronavirus outbreak ,therapy ,biology ,Coronavirus disease 2019 (COVID-19) ,medicine.drug_class ,business.industry ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,equine antibodies ,COVID-19 ,Brief Research Report ,Monoclonal antibody ,Virology ,Neutralization ,PRNT titers 50 ,Polyclonal antibodies ,biology.protein ,medicine ,Medicine ,Antibody ,business ,variant of concern ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit ,neutralization test - Abstract
SARS-CoV-2 variants of concern show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies; therefore, treatment alternatives are needed. We tested therapeutic equine polyclonal antibodies (pAbs) that are being assessed in clinical trials in Costa Rica against five globally circulating variants of concern: alpha, beta, epsilon, gamma and delta, using plaque reduction neutralization assays. We show that equine pAbs efficiently neutralize the variants of concern, with inhibitory concentrations in the range of 0.146-1.078 ��g/mL, which correspond to extremely low concentrations when compared to pAbs doses used in clinical trials. Equine pAbs are an effective, broad coverage, low-cost and a scalable COVID-19 treatment.
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- 2021
12. Science advisers around the world on 2020
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Emmanuel André, Eugenia Corrales-Aguilar, Chien-jen Chen, Mona Nemer, Gordon A. Awandare, Ligita Jancoriene, and Mohammed A. Mostajo-Radji
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Economic growth ,medicine.medical_specialty ,Government ,2019-20 coronavirus outbreak ,Multidisciplinary ,Coronavirus disease 2019 (COVID-19) ,Public health ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Political science ,Pandemic ,medicine - Abstract
Seven government researchers who helped to guide their governments’ responses to the COVID-19 pandemic speak out. Seven government researchers who helped to guide their governments’ responses to the COVID-19 pandemic speak out.
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- 2020
13. Heterologous Hyperimmune Polyclonal Antibodies Against SARS-CoV-2: A Broad Coverage, Affordable, and Scalable Potential Immunotherapy for COVID-19
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Alberto Alape-Girón, Andrés Moreira-Soto, Mauricio Arguedas, Hebleen Brenes, Willem Buján, Eugenia Corrales-Aguilar, Cecilia Díaz, Ann Echeverri, Marietta Flores-Díaz, Aarón Gómez, Andrés Hernández, María Herrera, Guillermo León, Román Macaya, José Arturo Molina-Mora, Javier Mora, Aarthi Narayanan, Alfredo Sanabria, Andrés Sánchez, Laura Sánchez, Álvaro Segura, Eduardo Segura, Daniela Solano, Claudio Soto, Jennifer L. Stynoski, Mariángela Vargas, Mauren Villalta, Jan Felix Drexler, and José María Gutiérrez
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2019-20 coronavirus outbreak ,Opinion ,Medicine (General) ,Convalescent plasma ,Coronavirus disease 2019 (COVID-19) ,medicine.drug_class ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine.medical_treatment ,Heterologous ,passive immunotherapy ,Monoclonal antibody ,Passive immunotherapy ,R5-920 ,heterologous antibodies ,Hyperimmune polyclonal antibodies ,Medicine ,biology ,business.industry ,SARS-CoV-2 ,COVID-19 ,General Medicine ,Immunotherapy ,Virology ,Polyclonal antibodies ,convalescent plasma ,biology.protein ,Heterologous antibodies ,Monoclonal antibodies ,monoclonal antibodies ,business ,hyperimmune polyclonal antibodies - Abstract
The emergence and dissemination of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic triggered a global public health crisis. Although several SARS-CoV-2 vaccines have been developed, demand far exceeds supply, access to them is inequitable, and thus, populations in low- and middle-income countries are unlikely to be protected soon (1). Furthermore, there are no specific therapies available, which is a challenge for COVID-19 patient care (2). Thus, the appearance of SARS-CoV-2 variants and reports of reinfections associated with immune escape (3, 4) highlight the urgent need for effective and broad coverage COVID-19 therapeutics. Intravenous administration of human or heterologous antibodies is a therapy successfully used in patients with viral respiratory diseases (5). Accordingly, formulations containing SARS-CoV-2 specific antibodies are an attractive therapeutic option for COVID-19 patients (6). SARS-CoV-2 specific antibodies could limit infection by direct virion neutralization and/or by targeting infected cells for elimination via complement or antibody-mediated cytotoxicity (6). Specific SARS-CoV-2 antibody-based therapeutics include convalescent plasma (CP), monoclonal antibodies (mAbs), human polyclonal IgG formulations purified from CP or transgenic animals, and heterologous hyperimmune polyclonal antibodies (pAbs) (6). Although the window for using antibody-based therapeutics varies, clinical data show that they are mainly effective if administered early after symptoms onset (6). Universidad de Costa Rica/[741-C0-198]/UCR/Costa Rica Caja Costarricense del Seguro Social/[]/CCSS/Costa Rica Banco Centroamericano de Integración Económica/[]/BCIE/Costa Rica German academic exchange services/[57592642]/DAAD/Alemania UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP) UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicina UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET)
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- 2021
14. In Vitro Inhibition of Zika Virus Replication with Amantadine and Rimantadine Hydrochlorides
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Francisco Vega-Aguilar, Dihalá Picado-Soto, Jorge L. Arias-Arias, Gilbert D. Loría, and Eugenia Corrales-Aguilar
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Microbiology (medical) ,Rimantadine ,viruses ,rimantadine ,Biology ,Dengue virus ,medicine.disease_cause ,Microbiology ,Virus ,yellow fever ,Dengue fever ,Zika virus ,Zika ,antivirals ,medicine ,Influenza A virus ,Molecular Biology ,amantadine ,Amantadine ,medicine.disease ,biology.organism_classification ,dengue ,Virology ,QR1-502 ,virology ,Flavivirus ,adamantanes ,medicine.drug - Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus in which human infection became relevant during recent outbreaks in Latin America due to its unrecognized association with fetal neurological disorders. Currently, there are no approved effective antivirals or vaccines for the treatment or prevention of ZIKV infections. Amantadine and rimantadine are approved antivirals used against susceptible influenza A virus infections that have been shown to have antiviral activity against other viruses, such as dengue virus (DENV). Here, we report the in vitro effectiveness of both amantadine and rimantadine hydrochlorides against ZIKV replication, resulting in a dose-dependent reduction in viral titers of a ZIKV clinical isolate and two different ZIKV reference strains. Additionally, we demonstrate similar in vitro antiviral activity of these drugs against DENV-1 and yellow fever virus (YFV), although at higher drug concentrations for the latter. ZIKV replication was inhibited at drug concentrations well below cytotoxic levels of both compounds, as denoted by the high selectivity indexes obtained with the tested strains. Further work is absolutely needed to determine the potential clinical use of these antivirals against ZIKV infections, but our results suggest the existence of a highly conserved mechanism across flavivirus, susceptible to be blocked by modified more specific adamantane compounds. Centro de Investigación en Enfermedades Tropicales, Facultad de Microbiología, Universidad de Costa Rica UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET) UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiología
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- 2021
15. Development and characterization of two equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19
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Alberto Alape, José María Gutiérrez, Guillermo León, Mauren Villalta, J. M. Gutierrez, Adriana Sánchez, Andrés Sánchez, Mauricio Arguedas, Edwin Moscoso, Mariángela Vargas, Aarthi Narayanan, Gabriela Solano, Laura Sánchez, María Herrera, Eugenia Corrales-Aguilar, Ana Cecilia Castillo, Maykel Cerdas, Ronald Sánchez, Andrés Hernández, Aarón Gómez, Cecilia Díaz, Deibid Umaña, Daniel Cordero, Ricardo Estrada, Charles L. Bailey, Gina Durán, Kenneth Risner, Álvaro Segura, M. M. Méndez, Eduardo Segura, and Daniela Solano
- Subjects
Science ,Enzyme-Linked Immunosorbent Assay ,Pharmacology ,Antibodies, Viral ,Article ,Immunoglobulin G ,law.invention ,Applied immunology ,law ,Animals ,Coronavirus Nucleocapsid Proteins ,Humans ,Medicine ,Horses ,Snake antivenom ,COVID-19 Serotherapy ,Multidisciplinary ,biology ,SARS-CoV-2 ,business.industry ,Immunochemistry ,Immunization, Passive ,COVID-19 ,Outbreak ,Antibodies, Neutralizing ,Recombinant Proteins ,In vitro ,Clinical trial ,Antiviral agents ,Polyclonal antibodies ,Spike Glycoprotein, Coronavirus ,biology.protein ,Recombinant DNA ,Immunization ,Antibody therapy ,Antibody ,business - Abstract
In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited high in vitro neutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.
- Published
- 2021
16. Serosurvey of Nonhuman Primates in Costa Rica at the Human-Wildlife Interface Reveals High Exposure to Flaviviruses
- Author
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Andrea Chaves, Carlos N. Ibarra-Cerdeña, Eugenia Corrales-Aguilar, Andres Moreira-Soto, Martha Piche-Ovares, Gerardo Suzán, and Gustavo A. Gutiérrez-Espeleta
- Subjects
DENGUE ,Science ,viruses ,VIRUSES ,sylvatic cycles ,030231 tropical medicine ,serology ,Dengue virus ,medicine.disease_cause ,Article ,Virus ,Dengue fever ,Zika virus ,03 medical and health sciences ,0302 clinical medicine ,flavivirus ,neotropical non-human primates ,medicine ,Flavivirus Infections ,COSTA RICA ,030304 developmental biology ,0303 health sciences ,dengue virus ,biology ,Yellow fever ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,PRIMATES ,biology.organism_classification ,medicine.disease ,Virology ,Flavivirus ,Insect Science ,Saint Louis encephalitis ,VIRUS ,West Nile virus ,Saint Louis encephalitis virus - Abstract
Acknowledgments: We are grateful to all contributors who assisted with sampling endeavors. We would also like to thank the National System of Conservation Areas (SINAC) and the Ministry of Environment and Energy (MINAE) of Costa Rica. We thank the Arbovirus Reference Collection (ARC) from the Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases, Arboviral Diseases Branch, Diagnostic and Reference Team, Reference and Reagent Laboratory, and Sanofi Pasteur for supplying the chimeric viruses Arthropod-borne viruses belonging to the flavivirus genus possess an enormous relevance in public health. Neotropical non-human primates (NPs) have been proposed to be susceptible to flavivirus infections due to their arboreal and diurnal habits, their genetic similarity to humans, and their relative closeness to humans. However, the only known flavivirus in the American continent maintained by sylvatic cycles involving NPs is yellow fever virus (YFV), and NPs’ role as potential hosts of other flaviviruses is still unknown. Here, we examined flavivirus exposure in 86 serum samples including 83.7% samples from free-range and 16.3% from captive NPs living in flavivirus- endemic regions of Costa Rica. Serum samples were opportunistically collected throughout Costa Rica in 2000–2015. We used a highly specific micro-plaque reduction neutralization test (micro-PRNT) to determine the presence of antibodies against YFV, dengue virus 1–4 (DENV), Zika virus, West Nile virus (WNV), and Saint Louis encephalitis virus (SLEV). We found evidence of seropositive NPs with homotypic reactivity to SLEV 11.6% (10/86), DENV 10.5% (9/86), and WNV 2.3% (2/86). Heterotypic reactivity was determined in 3.5% (3/86) of individuals against DENV, 1.2% (1/86) against SLEV, and 1.2% (1/86) against WNV. We found that 13.9% (12/86) of NPs were positive for an undetermined flavivirus species. No antibodies against DENV-3, DENV-4, YFV, or ZIKV were found. This work provides compelling serological evidence of flavivirus exposure in Costa Rican NPs, in particular to DENV, SLEV, and WNV. The range of years of sampling and the region from where positives were detected coincide with those in which peaks of DENV in human populations were registered, suggesting bidirectional exposure due to human–wildlife contact or bridging vectors. Our work suggests the continuous exposure of wildlife populations to various flaviviruses of public health importance and underscores the necessity of further surveillance of flaviviruses at the human–wildlife interface in Central America. Los virus transmitidos por artrópodos pertenecientes al género flavivirus tienen una enorme relevancia en la salud pública. Se ha propuesto que los primates neotropicales no humanos (PN) sean susceptibles a flavivirus debido a sus hábitos arborícolas y diurnos, a su similitud genética con los seres humanos y a su relativa cercanía con ellos. su relativa cercanía a los humanos. Sin embargo, el único flavivirus conocido en el continente americano de la fiebre amarilla es el único flavivirus conocido en el continente americano que se mantiene mediante ciclos silvícolas en los que participan los PN, y el papel de los PN como posibles de otros flavivirus es aún desconocido. Aquí examinamos la exposición a flavivirus en 86 muestras de suero suero, incluyendo un 83,7% de muestras de PN en libertad y un 16,3% de PN en cautividad que viven en regiones endémicas de flavivirus en Costa Rica. de flavivirus en regiones endémicas de Costa Rica. Las muestras de suero se recogieron de forma oportunista en toda Costa Rica en 2000-2015. Se utilizó una prueba de neutralización por reducción de microplaca altamente específica (micro-PRNT) para determinar la presencia de anticuerpos contra el YFV, el virus del dengue 1-4 (DENV), el virus del Zika, el virus del Nilo Occidental (WNV) y el virus de la encefalitis de San Luis (SLEV). Encontramos pruebas de PN seropositivas con reactividad homotípica al SLEV 11,6% (10/86), al DENV 10,5% (9/86) y al WNV 2,3% (2/86). La reactividad heterotípica heterotípica se determinó en el 3,5% (3/86) de los individuos contra el DENV, el 1,2% (1/86) contra el SLEV y el 1,2% (1/86) contra el VN. El 13,9% (12/86) de los PN fueron positivos para una especie indeterminada de especie indeterminada de flavivirus. No se encontraron anticuerpos contra el DENV-3, el DENV-4, el YFV o el ZIKV. Este trabajo proporciona pruebas serológicas convincentes de la exposición a flavivirus en los PN de Costa Rica, en particular a DENV, SLEV y WNV. El rango de años de muestreo y la región de donde se detectaron los positivos fueron detectados coinciden con aquellos en los que se registraron picos de DENV en poblaciones humanas, lo que sugiere una exposición bidireccional debida al contacto entre humanos y animales salvajes o a vectores puente. Nuestro trabajo Nuestro trabajo sugiere la exposición continua de las poblaciones silvestres a diversos flavivirus de importancia para la salud pública y subraya la necesidad de de salud pública y subraya la necesidad de una mayor vigilancia de los flavivirus en la interfaz hombre-vida silvestre en Centroamérica. en la interfaz hombre-vida silvestre en Centroamérica. Escuela de Medicina Veterinaria
- Published
- 2021
17. SARS-CoV-2 Genomic Surveillance in Costa Rica: Evidence of a Divergent Population and an Increased Detection of a Spike T1117I Mutation
- Author
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Cristian Pérez-Corrales, Jose Arturo Molina-Mora, Coingesa-Cr Consorcio Interinstitucional de Estudios Genómicos del SARS-CoV Costa Rica, Melany Calderón, Estela Cordero-Laurent, Hebleen Brenes, Jan Felix Drexler, Adriana Godínez, Claudio Soto-Garita, Andres Moreira-Soto, Eugenia Corrales-Aguilar, and Francisco Duarte-Martínez
- Subjects
Genetics ,education.field_of_study ,Mutation ,Lineage (genetic) ,Phylogenetic tree ,Population ,Outbreak ,Biology ,medicine.disease_cause ,Genome ,Pandemic ,medicine ,education ,Synonymous substitution - Abstract
Genome sequencing is a key strategy in the surveillance of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Latin America is the hardest hit region of the world, accumulating almost 20% of COVID-19 cases worldwide. Costa Rica was first exemplary for the region in its pandemic control, declaring a swift state of emergency on March 16th that led to a low quantity of cases, until measures were lifted in early May. From the first detected case in March 6th to December 31st almost 170 000 cases have been reported in Costa Rica, 99.5% of them from May onwards. We analyzed the genomic variability during the SARS-CoV-2 pandemic in Costa Rica using 185 sequences, 52 from the first months of the pandemic, and 133 from the current wave.Three GISAID clades (G, GH, and GR) and three PANGOLIN lineages (B.1, B.1.1, and B.1.291) are predominant, with phylogenetic relationships that are in line with the results of other Latin American countries, suggesting introduction and multiple re-introductions from other regions of the world. The whole-genome variant calling analysis identified a total of 283 distinct nucleotide variants. These correspond mostly to non-synonymous mutations (51.6%, 146) but 45.6% (129) corresponded to synonymous mutations. The 283 variants showed an expected power-law distribution: 190 single nucleotide mutations were identified in single sequences, only 16 single nucleotide mutations were found in >5% sequences, and only two mutations in >50% genomes. These mutations were distributed through the whole genome. However, 63.6% were present in ORF1ab, 11.7% in Spike gene and 10.6% in the Nucleocapsid gene. Additionally, the prevalence of worldwide-found variant D614G in the Spike (98.9% in Costa Rica), ORF8 L84S (1.1%) is similar to what is found elsewhere. Interestingly, the frequency of mutation T1117I in the Spike has increased during the current pandemic wave beginning in May 2020 in Costa Rica, reaching 29.2% detection in the full genome analyses in November 2020. This variant has been observed in less than 1% of the GISAID reported sequences worldwide in all the 2020. Structural modeling of the Spike protein with the T1117I mutation suggest a potential effect on the viral oligomerization needed for cell infection, but no differences with other genomes on transmissibility, severity nor vaccine effectiveness are predicted. Nevertheless, in-vitro experiments are required to support these in-silico findings. In conclusion, genome analyses of the SARS-CoV-2 sequences over the course of COVID-19 pandemic in Costa Rica suggest introduction of lineages from other countries as travel bans and measures were lifted, similar to results found in other studies, as well as an increase in the Spike-T1117I variant that needs to be monitored and studied in further analyses as part of the surveillance program during the pandemic.
- Published
- 2020
18. Susceptibility of well-differentiated airway epithelial cell cultures from domestic and wildlife animals to SARS-CoV-2
- Author
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Tran Thi Nhu Thao, Annika Kratzel, Ronald Dijkman, Nadine Ebert, Gergely Tekes, Bevan Sawatsky, Melle Holwerda, Jasmine Portmann, Laura Laloli, Horst Posthaus, Mitra Gultom, Manon Wider, Nadine Regenscheit, Volker Thiel, Eugenia Corrales Aguilar, Nicolas Ruggli, Veronika von Messling, Silvio Steiner, Amanda Vicente Santos, Hanspeter Stalder, Matthias Licheri, Andres Moreira Soto, Marina Straessle, Patrik Zanolari, Simone Schuller, and Corinne Gurtner
- Subjects
CATS ,Host (biology) ,viruses ,Wildlife ,respiratory system ,Biology ,Virology ,Epithelium ,Virus ,respiratory tract diseases ,medicine.anatomical_structure ,medicine ,Animal testing ,Domestication ,Airway - Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally, and the number of cases continues to rise all over the world. Besides humans, the zoonotic origin, as well as intermediate and potential spillback host reservoirs of SARS-CoV-2 are unknown. To circumvent ethical and experimental constraints, and more importantly, to reduce and refine animal experimentation, we employed our airway epithelial cell (AEC) culture repository composed of various domesticated and wildlife animal species to assess their susceptibility to SARS-CoV-2. In this study, we inoculated well-differentiated animal AEC cultures of monkey, cat, ferret, dog, rabbit, pig, cattle, goat, llama, camel, and two neotropical bat species with SARS-CoV-2. We observed that SARS-CoV-2 only replicated efficiently in monkey and cat AEC culture models. Whole-genome sequencing of progeny virus revealed no obvious signs of nucleotide transitions required for SARS-CoV-2 to productively infect monkey and cat epithelial airway cells. Our findings, together with the previously reported human-to-animal spillover events warrants close surveillance to understand the potential role of cats, monkeys, and closely related species as spillback reservoirs for SARS-CoV-2.
- Published
- 2020
19. Development and pre-clinical characterization of two therapeutic equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19
- Author
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Mariángela Vargas, Ricardo Estrada, Charles L. Bailey, Kenneth Risner, Ana Cecilia Castillo, Álvaro Segura, Adriana Sánchez, Gabriela Solano, Mauren Villalta, Gina Durán, Guillermo León, Laura Sánchez, Edwin Moscoso, Deibid Umaña, M. M. Méndez, Mauricio Arguedas, Alberto Alape, José María Gutiérrez, Eugenia Corrales-Aguilar, Eduardo Segura, Maykel Cerdas, Aarón Gómez, Andrés Hernández, Daniela Solano, Andrés Sánchez, Aarthi Narayanan, J. M. Gutierrez, Daniel Cordero, Cecilia Díaz, and María Herrera
- Subjects
biology ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Outbreak ,Pharmacology ,In vitro ,law.invention ,Clinical trial ,law ,Polyclonal antibodies ,biology.protein ,Recombinant DNA ,Medicine ,Snake antivenom ,Antibody ,business - Abstract
In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited highin vitroneutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.
- Published
- 2020
20. Advances in Clinical Diagnosis and Management of Chikungunya Virus Infection
- Author
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Eugenia Corrales-Aguilar, Claudio Soto-Garita, Jean-Paul Carrera, and Sandra López-Vergès
- Subjects
0301 basic medicine ,Cultural Studies ,Linguistics and Language ,History ,medicine.medical_specialty ,030106 microbiology ,030231 tropical medicine ,Disease ,medicine.disease_cause ,Arbovirus ,Language and Linguistics ,Dengue fever ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Chikungunya ,Intensive care medicine ,business.industry ,virus diseases ,Outbreak ,medicine.disease ,Anthropology ,Clinical diagnosis ,Chikungunya Virus Infection ,Differential diagnosis ,business - Abstract
In this review, we attempt to give the reader an update on clinical diagnosis, management, and treatment of Chikungunya virus (CHIKV) infection regarding the course of the disease and the role of clinical laboratory. CHIKV infection evolves through three phases: acute, sub-acute, and chronic. Protocol for patient assessment and management should be in agreement with each phase requirements. Despite its benignity, CHIKV infection has shown an increase in severe cases during recent outbreaks. Among the most affected group are neonates, elderly population, and patients with co-morbidities. Furthermore, since CHIKV geographical distribution and clinical spectrum overlaps with other arboviruses, differential diagnosis becomes crucial for physicians to ensure good management and treatment for patients. In this review, we describe and compare the main symptoms, complications, and risk groups for CHIKV, Dengue (DENV), and Zika (ZIKV) infections, regarding key features will guide to an accurate diagnosis. CHIKV is an emergent and reemergent arbovirus that arrived in the Americas in 2014, causing thousands of infections. The acute febrile phase is similar to that of dengue but with a higher proportion of debilitating arthralgia that can persist for months or even years after infection. Severe forms of CHIKV infection can lead to chronic polyarthralgia, neurologic symptoms, or multiorgan failure. Treatment of CHIKV infection is mainly focused on supportive care, which includes the use of analgesic and anti-inflammatory medication, rehydration, and rest.
- Published
- 2018
21. Neotropical primary bat cell lines show restricted dengue virus replication
- Author
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Claudio Soto-Garita, Eugenia Corrales-Aguilar, and Andres Moreira-Soto
- Subjects
0301 basic medicine ,Serotype ,In vitro studies ,030231 tropical medicine ,Immunology ,Dengue virus ,Real-Time Polymerase Chain Reaction ,Serogroup ,Virus Replication ,medicine.disease_cause ,Microbiology ,616.921 Fiebre de dengue ,Cell Line ,Dengue fever ,Dengue ,03 medical and health sciences ,0302 clinical medicine ,Species Specificity ,Chiroptera ,Bats ,medicine ,Animals ,Immunology and Allergy ,Molossus sinaloae ,Artibeus ,General Veterinary ,biology ,General Medicine ,Dengue Virus ,biology.organism_classification ,medicine.disease ,Virology ,030104 developmental biology ,Infectious Diseases ,599.4 Chiroptera (Quirópteros, Murciélagos) ,Viral replication ,Viral infection ,biology.protein ,Desmodus rotundus ,Antibody - Abstract
Dengue is the most widespread arboviral disease affecting humans. Bats are recognized carriers of emerging viral zoonoses and have been proposed as dengue reservoirs, since RNA/NS1 and/or antiviral antibodies have been detected. Yet, experimental inoculation of Artibeus bats failed to show virus replication. This conflicting results prevent drawing further conclusions of whether bats sustain dengue infection. To test bat cellular permissivity to dengue infection, we established primary bat embryonic cells from diverse organs and tissues of Artibeus jamaicensis, Molossus sinaloae, and Desmodus rotundus. We observed a limited serotype-, organ-, and bat species- specific dengue susceptibility. Only some Molossusderived primary cells sustained poorly initial Dengue serotype-1 replication, though it was latter absent. To elucidate if Molossus bats may play a role in dengue replication, ecological or in vivo experiments must be performed. Taken together our results show that Dengue did not replicate efficiently in cell lines derived from Neotropical bat species. UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiología UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET)
- Published
- 2017
22. Sloths host Anhanga virus‐related phleboviruses across large distances in time and space
- Author
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Andrés Moreira-Soto, Judy Avey-Arroyo, Andrea Rasche, Edmilson F. de Oliveira Filho, Francisco Arroyo-Murillo, Carlo Fischer, Eugenia Corrales-Aguilar, Anna-Lena Sander, and Jan Felix Drexler
- Subjects
Costa Rica ,040301 veterinary sciences ,Choloepus didactylus ,Bradypus variegatus ,Vector Borne Diseases ,Zoology ,Arbovirus Infections ,Arbovirus ,Virus ,0403 veterinary science ,03 medical and health sciences ,biology.animal ,evolution ,medicine ,Animals ,phlebovirus ,Phylogeny ,030304 developmental biology ,0303 health sciences ,Geography ,General Veterinary ,General Immunology and Microbiology ,biology ,Phylogenetic tree ,Reverse Transcriptase Polymerase Chain Reaction ,Choloepus hoffmanni ,High-Throughput Nucleotide Sequencing ,sloths ,04 agricultural and veterinary sciences ,General Medicine ,Viral Load ,Sloth ,biology.organism_classification ,medicine.disease ,3. Good health ,penshurt virus ,arbovirus ,Phlebovirus ,Rapid Communications ,RNA, Viral ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit ,Rapid Communication ,Arboviruses ,Brazil - Abstract
Sloths are genetically and physiologically divergent mammals. Phleboviruses are major arthropod‐borne viruses (arboviruses) causing disease in humans and other animals globally. Sloths host arboviruses, but virus detections are scarce. A phlebovirus termed Anhanga virus (ANHV) was isolated from a Brazilian Linnaeus's two‐toed sloth (Choloepus didactylus) in 1962. Here, we investigated the presence of phleboviruses in sera sampled in 2014 from 74 Hoffmann's two‐toed (Choloepus hoffmanni, n = 65) and three‐toed (Bradypus variegatus, n = 9) sloths in Costa Rica by broadly reactive RT‐PCR. A clinically healthy adult Hoffmann's two‐toed sloth was infected with a phlebovirus. Viral load in this animal was high at 8.5 × 107 RNA copies/ml. The full coding sequence of the virus was determined by deep sequencing. Phylogenetic analyses and sequence distance comparisons revealed that the new sloth virus, likely representing a new phlebovirus species, provisionally named Penshurt virus (PEHV), was most closely related to ANHV, with amino acid identities of 93.1%, 84.6%, 94.7% and 89.0% in the translated L, M, N and NSs genes, respectively. Significantly more non‐synonymous mutations relative to ANHV occurred in the M gene encoding the viral glycoproteins and in the NSs gene encoding a putative interferon antagonist compared to L and N genes. This was compatible with viral adaptation to different sloth species and with micro‐evolutionary processes associated with immune evasion during the genealogy of sloth‐associated phleboviruses. However, gene‐wide mean dN/dS ratios were low at 0.02–0.15 and no sites showed significant evidence for positive selection, pointing to comparable selection pressures within sloth‐associated viruses and genetically related phleboviruses infecting hosts other than sloths. The detection of a new phlebovirus closely‐related to ANHV, in sloths from Costa Rica fifty years after and more than 3,000 km away from the isolation of ANHV confirmed the host associations of ANHV‐related phleboviruses with the two extant species of two‐toed sloths.
- Published
- 2019
23. Dengue Virus Infection of Primary Human Smooth Muscle Cells
- Author
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Laya Hun, Rodrigo Mora-Rodriguez, Gilbert D. Loría, Jorge L. Arias-Arias, Eugenia Corrales-Aguilar, and Francisco Vega-Aguilar
- Subjects
0301 basic medicine ,Permissiveness ,Vascular smooth muscle ,viruses ,030231 tropical medicine ,Myocytes, Smooth Muscle ,Primary Cell Culture ,Viral Plaque Assay ,Vascular problems ,Dengue virus ,Biology ,Infections ,medicine.disease_cause ,Kidney ,Serogroup ,Virus Replication ,Umbilical vein ,Umbilical Arteries ,Dengue fever ,Cell Line ,Dengue ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Virology ,medicine ,Human Umbilical Vein Endothelial Cells ,Myocyte ,Animals ,Humans ,Epithelial Cells ,Articles ,Dengue Virus ,Viral Load ,medicine.disease ,Macaca mulatta ,030104 developmental biology ,Infectious Diseases ,Smooth muscle cells ,Viral replication ,Parasitology - Abstract
Dengue virus (DENV) infection of humans is presently the most important arthropod-borne viral global threat, for which no suitable or reliable animal model exists. Reports addressing the effect of DENV on vascular components other than endothelial cells are lacking. Dengue virus infection of vascular smooth muscle cells, which play a physiological compensatory response to hypotension in arteries and arterioles, has not been characterized, thus precluding our understanding of the role of these vascular components in dengue pathogenesis. Therefore, we studied the permissiveness of primary human umbilical artery smooth muscle cells (HUASMC) to DENV 1-4 infection and compared with the infection in the previously reported primary human umbilical vein endothelial cells (HUVEC) and the classically used, non-transformed, and highly permissive Lilly Laboratories Cell-Monkey Kidney 2 cells. Our results show that HUASMC are susceptible and productive to infection with the four DENV serotypes, although to a lesser extent when compared with the other cell lines. This is the first report of DENV permissiveness in human smooth muscle cells, which might represent an unexplored pathophysiological contributor to the vascular collapse observed in severe human dengue infection. Universidad de Costa Rica/[803-A5-025]/UCR/Costa Rica UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiología UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET)
- Published
- 2018
24. SARS-CoV-2 genomic surveillance in Costa Rica: Evidence of a divergent population and an increased detection of a spike T1117I mutation
- Author
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Claudio Soto-Garita, Melany Calderón-Osorno, Eugenia Corrales-Aguilar, Hebleen Brenes, Jan Felix Drexler, Adriana Godínez, Estela Cordero-Laurent, Coingesa-Cr Consorcio Interinstitucional de Estudios Genómicos del SARS-CoV Costa Rica, Francisco Duarte-Martínez, Jose Arturo Molina-Mora, Andres Moreira-Soto, and Cristian Pérez-Corrales
- Subjects
0301 basic medicine ,Microbiology (medical) ,Costa Rica ,Male ,Models, Molecular ,Protein Conformation ,030106 microbiology ,Population ,Genomics ,Biology ,medicine.disease_cause ,Microbiology ,Genome ,DNA sequencing ,Virus ,03 medical and health sciences ,Genomic surveillance ,Pandemic ,Genetic variation ,Genetics ,medicine ,Humans ,COSTA RICA ,education ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,education.field_of_study ,Mutation ,SARS-CoV-2 ,COVID-19 ,Genetic Variation ,030104 developmental biology ,Infectious Diseases ,Population Surveillance ,Spike Glycoprotein, Coronavirus ,Female ,Research Paper - Abstract
Genome sequencing is a key strategy in the surveillance of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Latin America is the hardest-hit region of the world, accumulating almost 20% of COVID-19 cases worldwide. In Costa Rica, from the first detected case on March 6th to December 31st almost 170,000 cases have been reported. We analyzed the genomic variability during the SARS-CoV-2 pandemic in Costa Rica using 185 sequences, 52 from the first months of the pandemic, and 133 from the current wave. Three GISAID clades (G, GH, and GR) and three PANGOLIN lineages (B.1, B.1.1, and B.1.291) were predominant, suggesting multiple re-introductions from other regions. The whole-genome variant calling analysis identified a total of 283 distinct nucleotide variants, following a power-law distribution with 190 single nucleotide mutations in a single sequence, and only 16 mutations were found in >5% sequences. These mutations were distributed through the whole genome. The prevalence of worldwide-found variant D614G in the Spike (98.9% in Costa Rica), ORF8 L84S (1.1%) is similar to what is found elsewhere. Interestingly, the frequency of mutation T1117I in the Spike has increased during the current pandemic wave beginning in May 2020 in Costa Rica, reaching 29.2% detection in the full genome analyses in November 2020. This variant has been observed in less than 1% of the GISAID reported sequences worldwide in 2020. Structural modeling of the Spike protein with the T1117I mutation suggests a potential effect on the viral oligomerization needed for cell infection, but no differences with other genomes on transmissibility, severity nor vaccine effectiveness are predicted. In conclusion, genome analyses of the SARS-CoV-2 sequences over the course of the COVID-19 pandemic in Costa Rica suggest the introduction of lineages from other countries and the detection of mutations in line with other studies, but pointing out the local increase in the detection of Spike-T1117I variant. The genomic features of this virus need to be monitored and studied in further analyses as part of the surveillance program during the pandemic., Graphical abstract Unlabelled Image
- Published
- 2021
25. Highly individual patterns of virus-immune IgG effector responses in humans
- Author
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Mirko Trilling, Albert Zimmermann, Hartmut Hengel, Valeria Falcone, Eugenia Corrales-Aguilar, Ortwin Adams, Sabine Santibanez, and Henrike Reinhard
- Subjects
Male ,0301 basic medicine ,Human cytomegalovirus ,Antiviral IgG ,Medizin ,Cytomegalovirus ,Adaptive Immunity ,Immunoglobulin G ,0302 clinical medicine ,Immunology and Allergy ,Child ,Original Investigation ,Aged, 80 and over ,biology ,General Medicine ,Middle Aged ,Acquired immune system ,Healthy Volunteers ,Child, Preschool ,ELISA ,Female ,Adult ,Microbiology (medical) ,Adolescent ,Immunology ,Virus ,Measles virus ,Young Adult ,03 medical and health sciences ,Neutralization ,Immune system ,Immunity ,medicine ,Animals ,Humans ,Aged ,Receptors, IgG ,Infant ,biology.organism_classification ,medicine.disease ,FcγRs ,Virology ,030104 developmental biology ,Humoral immunity ,biology.protein ,030215 immunology - Abstract
t IgG responses are fundamental to adaptive immunity and document immunological memory of previous pathogen encounter. While specific antigen recognition is mediated by the variable F(ab′)2 domain of IgG, various effector functions become activated via the constant Fcγ part bridging IgG-opsonized targets to FcγR-expressing immune effector cells. Traditionally, neutralizing IgG is considered the most appropriate correlate of protective humoral immunity to viruses. However, evidence is increasing that antiviral IgG mediates protection to viruses via activation of FcγRs. Using a test system allowing quantitative detection of virus-immune IgG able to activate FcγRs, sera of healthy individuals and vaccinees were assessed with regard to two prototypical human pathogenic viruses: measles and human cytomegalovirus. Marked differences in the capacity of individuals to generate FcγRI-, FcγRIIand FcγRIII-activating responses were noted. Comparison of FcγR-activating IgG with neutralizing and ELISA IgG concentrations did not correlate for HCMV and only very poorly for MV. Since neither neutralizing IgG nor overall IgG responses faithfully predict the activation of FcγRs, only the simultaneous quantification of IgGs activating defined FcγRs will aid to delineate individual “immunograms” of virus IgG immunity. Such new multiparametric assessment of antiviral IgG qualities could be instrumental in defining correlates of protection and disease progression. Deutsche Forschungsgemeinschaft/[He 2526/6-2, GK1045]//Alemania Helmholtz Association/[VISTRIE VH-VI-242]// European Commission/[QLRT-2001-01112]// European Commission/[MRTN-CT-2005-019248]// UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET)
- Published
- 2016
26. Specific Mutations in the PB2 Protein of Influenza A Virus Compensate for the Lack of Efficient Interferon Antagonism of the NS1 Protein of Bat Influenza A-Like Viruses
- Author
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Amzie Pavlisin, Andres Moreira-Soto, Juan Ayllon, Shashank Tripathi, Martin Schwemmle, Eugenia Corrales-Aguilar, Carles Martínez-Romero, Ignacio Mena, Teresa Aydillo, Adolfo García-Sastre, and Amanda Vicente-Santos
- Subjects
0301 basic medicine ,viruses ,Immunology ,Virulence ,Hemagglutinin (influenza) ,Viral Nonstructural Proteins ,medicine.disease_cause ,Microbiology ,NS1 protein ,Virus ,law.invention ,Viral Proteins ,03 medical and health sciences ,Interferon ,law ,Virology ,medicine ,Influenza A virus ,Influenza viruses ,Humans ,Gene ,599.472 867 Chiroptera (Quirópteros, Murciélagos) ,030102 biochemistry & molecular biology ,biology ,Bat ,virus diseases ,HEK293 Cells ,030104 developmental biology ,A549 Cells ,Insect Science ,Mutation ,biology.protein ,Recombinant DNA ,Pathogenesis and Immunity ,Interferons ,Neuraminidase ,medicine.drug - Abstract
Recently, two new influenza A-like viruses have been discovered in bats, A/little yellow-shouldered bat/Guatemala/060/2010 (HL17NL10) and A/flat-faced bat/Peru/033/2010 (HL18NL11). The hemagglutinin (HA)-like (HL) and neuraminidase (NA)-like (NL) proteins of these viruses lack hemagglutination and neuraminidase activities, despite their sequence and structural homologies with the HA and NA proteins of conventional influenza A viruses. We have now investigated whether the NS1 proteins of the HL17NL10 and HL18NL11 viruses can functionally replace the NS1 protein of a conventional influenza A virus. For this purpose, we generated recombinant influenza A/Puerto Rico/8/1934 (PR8) H1N1 viruses containing the NS1 protein of the PR8 wild-type, HL17NL10, and HL18NL11 viruses. These viruses (r/NS1PR8, r/NS1HL17, and r/NS1HL18, respectively) were tested for replication in bat and nonbat mammalian cells and in mice. Our results demonstrate that the r/NS1HL17 and r/NS1HL18 viruses are attenuated in vitro and in vivo . However, the bat NS1 recombinant viruses showed a phenotype similar to that of the r/NS1PR8 virus in STAT1 −/− human A549 cells and mice, both in vitro and in vivo systems being unable to respond to interferon (IFN). Interestingly, multiple mouse passages of the r/NS1HL17 and r/NS1HL18 viruses resulted in selection of mutant viruses containing single amino acid mutations in the viral PB2 protein. In contrast to the parental viruses, virulence and IFN antagonism were restored in the selected PB2 mutants. Our results indicate that the NS1 protein of bat influenza A-like viruses is less efficient than the NS1 protein of its conventional influenza A virus NS1 counterpart in antagonizing the IFN response and that this deficiency can be overcome by the influenza virus PB2 protein. IMPORTANCE Significant gaps in our understanding of the basic features of the recently discovered bat influenza A-like viruses HL17NL10 and HL18NL11 remain. The basic biology of these unique viruses displays both similarities to and differences from the basic biology of conventional influenza A viruses. Here, we show that recombinant influenza A viruses containing the NS1 protein from HL17NL10 and HL18NL11 are attenuated. This attenuation was mediated by their inability to antagonize the type I IFN response. However, this deficiency could be compensated for by single amino acid replacements in the PB2 gene. Our results unravel a functional divergence between the NS1 proteins of bat influenza A-like and conventional influenza A viruses and demonstrate an interplay between the viral PB2 and NS1 proteins to antagonize IFN.
- Published
- 2018
27. Unexpected Functional Divergence of Bat Influenza Virus NS1 Proteins
- Author
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M. Juozapaitis, Benjamin G. Hale, Nikos Tsolakos, Martin Schwemmle, Hannah L. Turkington, Eugenia Corrales-Aguilar, University of Zurich, and Hale, B G
- Subjects
10028 Institute of Medical Virology ,0301 basic medicine ,Models, Molecular ,1109 Insect Science ,Protein Conformation ,viruses ,Viral Nonstructural Proteins ,medicine.disease_cause ,Disease Outbreaks ,Madin Darby Canine Kidney Cells ,Phosphatidylinositol 3-Kinases ,Interferon ,Chiroptera ,Bats ,Influenza A virus ,Genetics ,Virulence factors ,biology ,Effector ,2404 Microbiology ,3. Good health ,Virus-Cell Interactions ,Host-Pathogen Interactions ,influenza ,Metabolic Networks and Pathways ,medicine.drug ,Protein Binding ,Signal Transduction ,RNA virus ,Virulence Factors ,Immunology ,bats ,Mutagenesis (molecular biology technique) ,610 Medicine & health ,Microbiology ,Virus ,Cell Line ,03 medical and health sciences ,Dogs ,Orthomyxoviridae Infections ,Species Specificity ,Virology ,Influenza, Human ,medicine ,Animals ,Humans ,Protein Interaction Domains and Motifs ,AKT signaling ,Gene ,RNA, Double-Stranded ,2403 Immunology ,Base Sequence ,biology.organism_classification ,Influenza ,030104 developmental biology ,HEK293 Cells ,Amino Acid Substitution ,A549 Cells ,Insect Science ,2406 Virology ,570 Life sciences ,Proto-Oncogene Proteins c-akt ,Functional divergence - Abstract
Recently, two influenza A virus (FLUAV) genomes were identified in Central and South American bats. These sequences exhibit notable divergence from classical FLUAV counterparts, and functionally, bat FLUAV glycoproteins lack canonical receptor binding and destroying activity. Nevertheless, other features that distinguish these viruses from classical FLUAVs have yet to be explored. Here, we studied the viral nonstructural protein NS1, a virulence factor that modulates host signaling to promote efficient propagation. Like all FLUAV NS1 proteins, bat FLUAV NS1s bind double-stranded RNA and act as interferon antagonists. Unexpectedly, we found that bat FLUAV NS1s are unique in being unable to bind host p85β, a regulatory subunit of the cellular metabolism-regulating enzyme, phosphoinositide 3-kinase (PI3K). Furthermore, neither bat FLUAV NS1 alone nor infection with a chimeric bat FLUAV efficiently activates Akt, a PI3K effector. Structure-guided mutagenesis revealed that the bat FLUAV NS1-p85β interaction can be reengineered (in a strain-specific manner) by changing two to four NS1 residues (96L, 99M, 100I, and 145T), thereby creating a hydrophobic patch. Notably, ameliorated p85β-binding is insufficient for bat FLUAV NS1 to activate PI3K, and a chimeric bat FLUAV expressing NS1 with engineered hydrophobic patch mutations exhibits cell-type-dependent, but species-independent, propagation phenotypes. We hypothesize that bat FLUAV hijacking of PI3K in the natural bat host has been selected against, perhaps because genes in this metabolic pathway were differentially shaped by evolution to suit the unique energy use strategies of this flying mammal. These data expand our understanding of the enigmatic functional divergence between bat FLUAVs and classical mammalian and avian FLUAVs. IMPORTANCE The potential for novel influenza A viruses to establish infections in humans from animals is a source of continuous concern due to possible severe outbreaks or pandemics. The recent discovery of influenza A-like viruses in bats has raised questions over whether these entities could be a threat to humans. Understanding unique properties of the newly described bat influenza A-like viruses, such as their mechanisms to infect cells or how they manipulate host functions, is critical to assess their likelihood of causing disease. Here, we characterized the bat influenza A-like virus NS1 protein, a key virulence factor, and found unexpected functional divergence of this protein from counterparts in other influenza A viruses. Our study dissects the molecular changes required by bat influenza A-like virus NS1 to adopt classical influenza A virus properties and suggests consequences of bat influenza A-like virus infection, potential future evolutionary trajectories, and intriguing virus-host biology in bat species.
- Published
- 2017
28. Pathogenic potential of a Costa Rican strain of ‘Candidatus Rickettsia amblyommii’ in guinea pigs (Cavia porcellus) and protective immunity against Rickettsia rickettsii
- Author
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Adriana Troyo, Laya Hun, Gilberth Alvarado, Olger Calderón-Arguedas, Lizeth Taylor, Juan Alberto Morales, Eugenia Corrales-Aguilar, Andres Moreira-Soto, and Juan J. Rivas
- Subjects
Costa Rica ,Male ,Rocky Mountain spotted fever ,Guinea Pigs ,RICKETTSIA AMBLYOMMII ,EXPERIMENTAL INFECTION ,Cavia ,IMMUNITY ,579.327 Rickettsias y Chlamydias ,Microbiology ,Serology ,INMUNOLOGÍA VETERINARIA ,GUINEA PIG ,medicine ,Animals ,COSTA RICA ,Rickettsia ,biology ,Rickettsia Infections ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,medicine.disease ,Rickettsia rickettsii ,Antibodies, Bacterial ,Virology ,INMUNOLOGÍA ,Spotted fever ,Titer ,Infectious Diseases ,Immunoglobulin G ,Insect Science ,Candidatus ,bacteria ,Parasitology - Abstract
Candidatus Rickettsia amblyommii' is a spotted fever group rickettsia that is not considered pathogenic, although there is serologic evidence of possible infection in animals and humans. The aim of this study was to evaluate the pathogenic potential of a Costa Rican strain of ' Candidatus R. amblyommii' in guinea pigs and determine its capacity to generate protective immunity against a subsequent infection with a local strain of Rickettsia rickettsii isolated from a human case. Six guinea pigs were inoculated with ' Candidatus R. amblyommii' strain 9-CC-3-1 and two controls with cell culture medium. Health status was evaluated, and necropsies were executed at days 2, 4, and 13. Blood and tissues were processed by PCR to detect the gltA gene, and end titers of anti-' Candidatus R. amblyommii' IgG were determined by indirect immunofluorescence. To evaluate protective immunity, another 5 guinea pigs were infected with ' Candidatus R. amblyommii' (IGPs). After 4 weeks, these 5 IGPs and 3 controls (CGPs) were inoculated with pathogenic R. rickettsii. Clinical signs and titers of anti-. Rickettsia IgG were determined. IgG titers reached 1:512 at day 13 post-infection with ' Candidatus R. amblyommii' On day 2 after inoculation, two guinea pigs had enlarged testicles and ' Candidatus R. amblyommii' DNA was detected in testicles. Histopathology confirmed piogranulomatous orchitis with perivascular inflammatory infiltrate in the epididymis. In the protective immunity assay, anti-. Rickettsia IgG end titers after R. rickettsii infection were lower in IGPs than in CGPs. IGPs exhibited only transient fever, while CGP showed signs of severe disease and mortality. R. rickettsii was detected in testicles and blood of CGPs. Results show that the strain 9-CC-3-1 of ' Candidatus R. amblyommii' was able to generate pathology and an antibody response in guinea pigs. Moreover, its capacity to generate protective immunity against R. rickettsii may modulate the epidemiology and severity of Rocky Mountain spotted fever in areas where both species circulate. Candidatus Rickettsia amblyommii' es un grupo de fiebre maculosa rickettsia que no se considera patógena, aunque existen pruebas serológicas de una posible infección en animales y seres humanos. El objetivo de este estudio fue evaluar el potencial patógeno de una cepa costarricense de ' Candidatus R. amblyommii' en conejillos de indias y determinar su capacidad para generar inmunidad protectora contra una infección posterior con una cepa local de Rickettsia rickettsii aislada de un caso humano. Se inocularon seis cobayas con la cepa 9-CC-3-1 de ' Candidatus R. amblyommii' y dos controles con medio de cultivo celular. Se evaluó el estado de salud y se realizaron necropsias en los días 2, 4 y 13. La sangre y los tejidos fueron procesados por PCR para detectar el gen gltA, y los títulos finales de la IgG de ' Candidatus R. amblyommii' fueron determinados por inmunofluorescencia indirecta. Para evaluar la inmunidad protectora, otros 5 conejillos de indias fueron infectados con ' Candidatus R. amblyommii' (IGP). Después de 4 semanas, estos 5 IGP y 3 controles (CGP) fueron inoculados con R. rickettsii patógeno. Los signos clínicos y los títulos de anti. Rickettsia IgG fueron determinados. Los títulos de IgG alcanzaron 1:512 en el día 13 después de la infección con ' Candidatus R. amblyommii' El día 2 después de la inoculación, dos conejillos de indias tenían los testículos agrandados y el ADN de ' Candidatus R. amblyommii' fue detectado en los testículos. La histopatología confirmó la orquitis piogranulomatosa con infiltrado inflamatorio perivascular en el epidídimo. En el ensayo de inmunidad protectora, el anti. Los títulos finales de IgG de Rickettsia después de la infección de R. rickettsii fueron menores en los IGP que en los CGP. Los IGP sólo mostraron fiebre transitoria, mientras que los CGP mostraron signos de enfermedad grave y mortalidad. R. rickettsii se detectó en los testículos y en la sangre de los CGP. Los resultados muestran que la cepa 9-CC-3-1 de ' Candidatus R. amblyommii' fue capaz de generar una patología y una respuesta de anticuerpos en los conejillos de indias. Además, su capacidad de generar inmunidad protectora contra R. rickettsii puede modular la epidemiología y la gravedad de la fiebre maculosa de las Montañas Rocosas en las zonas donde circulan ambas especies. Universidad Nacional, Costa Rica Escuela de Medicina Veterinaria
- Published
- 2015
29. Neotropical bats that co-habit with humans function as dead-end hosts for dengue virus
- Author
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Amanda Vicente-Santos, Andres Moreira-Soto, Jan Felix Drexler, Andrea Chaves, Juan Morales, Bernal Rodríguez-Herrera, Luis Guillermo Chaverri, Eugenia Corrales-Aguilar, Claudio Soto-Garita, and Alejandro Alfaro-Alarcón
- Subjects
Male ,Serotype ,Urban Population ,TROPICAL FORESTS ,Artificial Gene Amplification and Extension ,Dengue virus ,Pathology and Laboratory Medicine ,Antibodies, Viral ,Biochemistry ,Polymerase Chain Reaction ,0302 clinical medicine ,Seroepidemiologic Studies ,Chiroptera ,Bats ,biology.owned_animal ,Mammals ,Immunoassay ,Cytochrome b ,Phylogenetic Analysis ,3. Good health ,BOSQUES TROPICALES ,Blood ,599.4 Chiroptera (Quirópteros, Murciélagos) ,Medical Microbiology ,Viral Pathogens ,VIRUS ,Viral load ,Costa Rica ,lcsh:RC955-962 ,Immunology ,Microbiology ,03 medical and health sciences ,Humans ,Evolutionary Systematics ,Molecular Biology Techniques ,Molecular Biology ,Microbial Pathogens ,Flaviviruses ,Organisms ,Public Health, Environmental and Occupational Health ,Biology and Life Sciences ,Proteins ,Murcielago ,lcsh:RA1-1270 ,Dengue Virus ,medicine.disease ,Invertebrates ,Virology ,Insect Vectors ,Species Interactions ,030104 developmental biology ,RNA viruses ,0301 basic medicine ,Physiology ,viruses ,Disease Vectors ,Wildlife ,medicine.disease_cause ,Mosquitoes ,Dengue fever ,Immune Physiology ,Medicine and Health Sciences ,Data Management ,Immune System Proteins ,Reverse Transcriptase Polymerase Chain Reaction ,lcsh:Public aspects of medicine ,Viral Load ,Body Fluids ,Insects ,Phylogenetics ,Infectious Diseases ,Vertebrates ,Viruses ,RNA, Viral ,Female ,Anatomy ,Pathogens ,Research Article ,Computer and Information Sciences ,DENGUE ,lcsh:Arctic medicine. Tropical medicine ,Arthropoda ,Animal Types ,030231 tropical medicine ,Dead end hosts ,Biology ,Research and Analysis Methods ,Antibodies ,Virus ,medicine ,Animals ,Seroprevalence ,Taxonomy ,Evolutionary Biology ,Animal Structures ,MURCIÉLAGO ,Amniotes ,Zoology - Abstract
Several studies have shown Dengue Virus (DENV) nucleic acids and/or antibodies present in Neotropical wildlife including bats, suggesting that some bat species may be susceptible to DENV infection. Here we aim to elucidate the role of house-roosting bats in the DENV transmission cycle. Bats were sampled in households located in high and low dengue incidence regions during rainy and dry seasons in Costa Rica. We captured 318 bats from 12 different species in 29 households. Necropsies were performed in 205 bats to analyze virus presence in heart, lung, spleen, liver, intestine, kidney, and brain tissue. Histopathology studies from all organs showed no significant findings of disease or infection. Sera were analyzed by PRNT90 for a seroprevalence of 21.2% (51/241), and by PCR for 8.8% (28/318) positive bats for DENV RNA. From these 28 bats, 11 intestine samples were analyzed by RT-PCR. Two intestines were DENV RNA positive for the same dengue serotype detected in blood. Viral isolation from all positive organs or blood was unsuccessful. Additionally, viral load analyses in positive blood samples by qRT-PCR showed virus concentrations under the minimal dose required for mosquito infection. Simultaneously, 651 mosquitoes were collected using EVS-CO2 traps and analyzed for DENV and feeding preferences (bat cytochrome b). Only three mosquitoes were found DENV positive and none was positive for bat cytochrome b. Our results suggest an accidental presence of DENV in bats probably caused from oral ingestion of infected mosquitoes. Phylogenetic analyses suggest also a spillover event from humans to bats. Therefore, we conclude that bats in these urban environments do not sustain DENV amplification, they do not have a role as reservoirs, but function as epidemiological dead end hosts for this virus., Author summary Dengue is the most important human vector-borne disease. Several studies have shown DENV presence in mammalian wildlife such as bats, thus considering them putative reservoirs or hosts. We aimed to elucidate if bats that cohabit in houses in close proximity with humans may be involved in a dengue transmission cycle. We sampled bats in low and high dengue incidence areas during the dry (low mosquito abundance) and wet (high mosquito abundance) seasons. We analyzed blood and several organs. As previously reported, we found DENV nucleic acid and neutralizing antibodies in a small percentage of blood samples, but virus detection in all organs was negative. We were able to show that dengue found in all positive samples was in low concentration and thus virus isolation was unsuccessful. We found positive intestine samples which may suggest infection through DENV-positive mosquito ingestion. Furthermore, mosquitoes sampled in close vicinity of bats’ roosting place were not feeding on these mammals. Virus sequence analysis from bats and humans show a spillover effect from humans to bats. Taken together, our results indicate that bats do not sustain sufficient virus amplification in order to function as reservoirs and exclude them as players in the dengue virus transmission cycle.
- Published
- 2017
30. CMV-encoded Fcγ receptors: modulators at the interface of innate and adaptive immunity
- Author
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Katja Hoffmann, Eugenia Corrales-Aguilar, and Hartmut Hengel
- Subjects
Human cytomegalovirus ,Hyperimmune globulin ,IgG ,viruses ,Immunology ,Cytomegalovirus ,Adaptive Immunity ,Antibodies, Viral ,Ligands ,Immunoglobulin G ,Immunomodulation ,Viral Proteins ,Immune system ,Immunity ,medicine ,Animals ,Humans ,Immunology and Allergy ,Receptor ,Antibody-dependent cell-mediated cytotoxicity ,biology ,Immune evasion ,Receptors, IgG ,Acquired immune system ,medicine.disease ,FcγRs ,Virology ,Immunity, Innate ,Cytomegalovirus Infections ,biology.protein ,Immunotherapy ,ADCC ,Carrier Proteins ,Protein Binding - Abstract
The constant region of IgG antibodies mediates antiviral activities upon engaging host Fcγ receptors (FcγRs) expressed by a variety of immune cells, such as antibody-dependent cellullar cytotoxcity (ADCC) executed by natural killer (NK)cells. Human cytomegalovirus (HCMV) is unique among viruses by encoding also an array of several Fcγ-binding glycoproteins with cell surface disposition and concomitant incorporation into the virion. Evidence is increasing that the virus-encoded Fcγ receptors differ in their Fcγ binding mode but effectively operate as adversaries of host FcγRs since they are able to prevent IgG-mediated triggering of activating host FcγRs, i.e., FcγRI, FcγRIIA, and FcγRIIIA. Here we discuss virus-encoded FcγRs as the first known HCMV inhibitors of IgG-mediated immunity which could account for the limited efficacy of HCMV hyperimmune globulin in clinical settings. A better understanding of their molecular mode of action opens up new perspectives for improving IgG therapies against HCMV disease. DFG through He 2,526/6–2 European Commission through QLRT-2001–01112 European Commission through MRTN-CT-2005–019248 Helmholtz Association through VISTRIE VH-VI-242 UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiología
- Published
- 2014
31. Molecular Characterization of Two Major Dengue Outbreaks in Costa Rica
- Author
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Teresita Somogyi, Claudio Soto-Garita, Eugenia Corrales-Aguilar, and Amanda Vicente-Santos
- Subjects
Costa Rica ,0301 basic medicine ,Aedes albopictus ,Genotype ,viruses ,030231 tropical medicine ,Dengue virus ,medicine.disease_cause ,Disease Outbreaks ,Dengue fever ,Dengue ,03 medical and health sciences ,0302 clinical medicine ,Aedes aegypti ,Aedes ,Virology ,medicine ,Animals ,Humans ,Phylogeny ,biology ,Outbreak ,virus diseases ,Forestry ,Articles ,Dengue Virus ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,biology.organism_classification ,Insect Vectors ,Virus ,030104 developmental biology ,Infectious Diseases ,Geography ,RNA, Viral ,Parasitology - Abstract
Dengue virus (DENV) (Flavivirus, Flaviviridae) is a reemerging arthropod-borne virus with a worldwide circulation, transmitted mainly by Aedes aegypti and Aedes albopictus mosquitoes. Since the first detection of its main transmitting vector in 1992 and the invasion of DENV-1 in 1993, Costa Rica has faced dengue outbreaks yearly. In 2007 and 2013, Costa Rica experienced two of the largest outbreaks in terms of total and severe cases. To provide genetic information about the etiologic agents producing these outbreaks, we conducted phylogenetic analysis of viruses isolated from human samples. A total of 23 DENV-1 and DENV-2 sequences were characterized. These analyses signaled that DENV-1 genotype V and DENV-2 American/Asian genotype were circulating in those outbreaks. Our results suggest that the 2007 and 2013 outbreak viral strains of DENV-1 and DENV-2 originated from nearby countries and underwent in situ microevolution. UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET) UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiología
- Published
- 2016
32. Encefalitis arboviral en caballos de Costa Rica: 2009-2016
- Author
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Martha Piche, Aida J. Chaves, Carlos Jiménez, Bernal León, Alejandro Alfaro, Mario Romero, Sabine E. Hutter, Juan Morales, Mario Baldi, and Eugenia Corrales-Aguilar
- Subjects
Microbiology (medical) ,Arbovirus ,viruses ,CABALLOS ,virus diseases ,General Medicine ,medicine.disease ,HORSES ,Virology ,Infectious Diseases ,Geography ,Arboviral encephalitis ,medicine ,ENCEFALITIS ,VIRUS ,COSTA RICA ,Neurological disease - Abstract
Arbovirus of the genus Alphavirus and Flavivirus can cause febrile illness and sometimes neurological disease in both humans and animals. West Nile Virus (WNV), Eastern Equine Encephalitis Virus (EEEV), Western Equine Encephalitis Virus (WEEV) and Venezuelan Equine Encephalitis Virus (VEEV) are endemic in the Mesoamerican region and the local appearance of these viruses is regulated by the amount of vectors and reservoirs. The objective of this research was to establish the etiologic agents associated with the presentation of arboviral neurological disease in Costa Rican horses from 2009-2016. Los arbovirus del género Alphavirus y Flavivirus pueden causar enfermedades febriles y a veces neurológicas tanto en humanos como en animales. El virus del Nilo Occidental (VNO), el virus de la Encefalitis Equina Oriental (EEEV), Encefalitis Equina Occidental (WEEV) y (WEEV) y el virus de la encefalitis equina venezolana (VEEV) son endémicos en la región mesoamericana y la aparición local de estos virus está regulada por la cantidad de vectores y reservorios. El objetivo de esta investigación fue establecer los agentes etiológicos asociados a la presentación de la enfermedad neurológica arboviral neurológica arboviral en caballos costarricenses entre 2009 y 2016. Universidad Nacional, Costa Rica Escuela de Medicina Veterinaria
- Published
- 2016
33. Neotropical Bats from Costa Rica harbour Diverse Coronaviruses
- Author
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Carlos Jiménez, N. Vargas-Vargas, Andres Moreira-Soto, Bernal Rodríguez-Herrera, L. Taylor-Castillo, and Eugenia Corrales-Aguilar
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Costa Rica ,Epidemiology ,Short Communication ,viruses ,Short Communications ,Zoology ,Genome, Viral ,medicine.disease_cause ,Communicable Diseases, Emerging ,Homology (biology) ,Feces ,Phylogenetics ,Chiroptera ,Bats ,medicine ,Animals ,Humans ,Glossophaga soricina ,Phylogeny ,Artibeus ,Coronavirus ,Carollia perspicillata ,Phylogenetic analysis ,General Veterinary ,General Immunology and Microbiology ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Carollia castanea ,phylogenetic analysis ,CORONAVIRUSES ,Public Health, Environmental and Occupational Health ,Genetic Variation ,virus diseases ,Bayes Theorem ,biochemical phenomena, metabolism, and nutrition ,respiratory system ,RNA-Dependent RNA Polymerase ,biology.organism_classification ,respiratory tract diseases ,Infectious Diseases ,599.4 Chiroptera (Quirópteros, Murciélagos) ,mu ,MURCIELAGOS ,VIRUS ,Taxonomy (biology) ,Coronavirus Infections ,Sequence Analysis - Abstract
Bats are hosts of diverse coronaviruses (CoVs) known to potentially cross the host–species barrier. For analysing coronavirus diversity in a bat species-rich country, a total of 421 anal swabs/faecal samples from Costa Rican bats were screened for CoV RNA-dependent RNA polymerase (RdRp) gene sequences by a pancoronavirus PCR. Six families, 24 genera and 41 species of bats were analysed. The detection rate for CoV was 1%. Individuals (n = 4) from four different species of frugivorous (Artibeus jamaicensis, Carollia perspicillata and Carollia castanea) and nectivorous (Glossophaga soricina) bats were positive for coronavi- rus-derived nucleic acids. Analysis of 440 nt. RdRp sequences allocated all Costa Rican bat CoVs to the a-CoV group. Several CoVs sequences clustered near previously described CoVs from the same species of bat, but were phylogeneti- cally distant from the human CoV sequences identified to date, suggesting no recent spillover events. The Glossophaga soricina CoV sequence is sufficiently dis- similar (26% homology to the closest known bat CoVs) to represent a unique coronavirus not clustering near other CoVs found in the same bat species so far, implying an even higher CoV diversity than previously suspected. Los murciélagos son huéspedes de diversos coronavirus (CoV) que se sabe que pueden cruzar la la barrera de la especie huésped. Para analizar la diversidad de coronavirus en un país rico en especies de murciélagos de murciélagos, se analizaron 421 muestras de hisopos anales y heces de murciélagos costarricenses de la RNA polimerasa dependiente del CoV (RdRp) mediante una PCR de pancoronavirus. PCR de pancoronavirus. Se analizaron seis familias, 24 géneros y 41 especies de murciélagos. La tasa de detección del CoV fue del 1%. Se analizaron individuos (n = 4) de cuatro especies diferentes de murciélagos frugívoros (n = 4). especies de murciélagos frugívoros (Artibeus jamaicensis, Carollia perspicillata y Carollia castanea) y nectivoros (Glossophaga soricina) resultaron positivos a los ácidos nucleicos derivados del coronavi rus. El análisis de las secuencias de 440 nt. RdRp asignó todos los CoV de los murciélagos de Costa de Costa Rica al grupo a-CoV. Varias secuencias de CoVs se agruparon cerca de CoVs previamente descritos de la misma especie de murciélago, pero eran filogenéticamente distantes del CoV humano. de los CoV humanos identificados hasta la fecha, lo que sugiere que no se han producido de la contaminación reciente. La secuencia del CoV de Glossophaga soricina es lo suficientemente dis (26% de homología con los CoVs de murciélagos conocidos más cercanos) como para representar un único coronavirus que no se agrupa cerca de otros CoVs encontrados en la misma especie de murciélago hasta ahora, lo que implica una diversidad de CoV aún mayor de lo que se sospechaba. Universidad Nacional, Costa Rica Escuela de Medicina Veterinaria
- Published
- 2015
34. Human cytomegalovirus Fcγ binding proteins gp34 and gp68 antagonize Fcγ receptors I, II and III
- Author
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Mirko Trilling, Vu Thuy Khanh Le, Manuela Fiedler, Henrike Reinhard, Katja Hunold, Albert Zimmermann, David C. Johnson, Hartmut Hengel, Enver Aliyev, Eva Mercé-Maldonado, Eugenia Corrales-Aguilar, and Katrin Ehrhardt
- Subjects
Human cytomegalovirus ,viruses ,Medizin ,Cytomegalovirus ,Herpesvirus 1, Human ,Virus Replication ,Immunoglobulin G ,Chlorocebus aethiops ,lcsh:QH301-705.5 ,Cells, Cultured ,CD64 ,Membrane Glycoproteins ,biology ,Viral Immune Evasion ,virus diseases ,Host-Pathogen Interactions ,Protein Binding ,Research Article ,lcsh:Immunologic diseases. Allergy ,medicine.drug_class ,Immunology ,CD16 ,Monoclonal antibody ,Microbiology ,Viral Proteins ,Immune system ,Antigen ,Virology ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Glycoproteins ,Receptors, IgG ,Immunity ,Biology and Life Sciences ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Immunoglobulin Fc Fragments ,HEK293 Cells ,lcsh:Biology (General) ,Polyclonal antibodies ,Humoral Immunity ,biology.protein ,Parasitology ,lcsh:RC581-607 ,Carrier Proteins - Abstract
Human cytomegalovirus (HCMV) establishes lifelong infection with recurrent episodes of virus production and shedding despite the presence of adaptive immunological memory responses including HCMV immune immunoglobulin G (IgG). Very little is known how HCMV evades from humoral and cellular IgG-dependent immune responses, the latter being executed by cells expressing surface receptors for the Fc domain of IgG (FcγRs). Remarkably, HCMV expresses the RL11-encoded gp34 and UL119-118-encoded gp68 type I transmembrane glycoproteins which bind Fcγ with nanomolar affinity. Using a newly developed FcγR activation assay, we tested if the HCMV-encoded Fcγ binding proteins (HCMV FcγRs) interfere with individual host FcγRs. In absence of gp34 or/and gp68, HCMV elicited a much stronger activation of FcγRIIIA/CD16, FcγRIIA/CD32A and FcγRI/CD64 by polyclonal HCMV-immune IgG as compared to wildtype HCMV. gp34 and gp68 co-expression culminates in the late phase of HCMV replication coinciding with the emergence of surface HCMV antigens triggering FcγRIII/CD16 responses by polyclonal HCMV-immune IgG. The gp34- and gp68-dependent inhibition of HCMV immune IgG was fully reproduced when testing the activation of primary human NK cells. Their broad antagonistic function towards FcγRIIIA, FcγRIIA and FcγRI activation was also recapitulated in a gain-of-function approach based on humanized monoclonal antibodies (trastuzumab, rituximab) and isotypes of different IgG subclasses. Surface immune-precipitation showed that both HCMV-encoded Fcγ binding proteins have the capacity to bind trastuzumab antibody-HER2 antigen complexes demonstrating simultaneous linkage of immune IgG with antigen and the HCMV inhibitors on the plasma membrane. Our studies reveal a novel strategy by which viral FcγRs can compete for immune complexes against various Fc receptors on immune cells, dampening their activation and antiviral immunity., Author Summary Herpes viruses persist lifelong continuously alternating between latency and virus production and transmission. The latter events occur despite the presence of immune IgG antibodies. IgG acts by neutralization of virions and activation of immune cells bearing one or more surface receptors, called FcγRs, recognizing the constant Fc domain of IgG. Activating FcγRs induce a wide range of immune responses, including antibody dependent cellular cytotoxicity (ADCC) of virus-infected cells by natural killer (NK) cells, cytokine secretion and the uptake of immune complexes to enhance antigen presentation to T cells. We demonstrate that the HCMV glycoproteins RL11/gp34 and UL119-118/gp68 block IgG-mediated activation of FcγRs. A novel reporter cell-based assay was used to test FcγRs individually and assess their relative susceptibility to each antagonist. This approach revealed that gp34 and gp68 block triggering of activating FcγRs, i.e. FcγRI (CD64), FcγRII (CD32A) and FcγRIII (CD16). Co-immunoprecipitation showed the formation of ternary complexes containing IgG, IgG-bound antigen and the viral antagonists on the cell surface. Assigning the redundant abilities of HCMV to hinder IgG effector responses to the viral Fc binding proteins, we discuss gp34 and gp68 as potential culprits which might contribute to the limited efficacy of therapeutic IgG against HCMV.
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- 2013
35. A novel assay for detecting virus-specific antibodies triggering activation of Fcγ receptors
- Author
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Marek Widera, Eugenia Corrales-Aguilar, Albert Zimmermann, Henrike Reinhard, Hartmut Hengel, Eva Mercé-Maldonado, Ofer Mandelboim, Mirko Trilling, and Heiner Schaal
- Subjects
Herpesvirus 4, Human ,CD3 Complex ,Recombinant Fusion Proteins ,Immunology ,Medizin ,Cytomegalovirus ,Enzyme-Linked Immunosorbent Assay ,Herpesvirus 1, Human ,Antibodies, Viral ,medicine.disease_cause ,Virus ,Antibodies ,Cell Line ,Measles virus ,Mice ,Immune system ,Cell Line, Tumor ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Immunology and Allergy ,Receptor ,Vero Cells ,Cell Line, Transformed ,Antibody-dependent cell-mediated cytotoxicity ,Viral infections ,Hybridomas ,biology ,Fcγ receptors ,Receptors, IgG ,U937 Cells ,biology.organism_classification ,Virology ,Molecular biology ,Coculture Techniques ,Killer Cells, Natural ,HEK293 Cells ,Herpes simplex virus ,IgG binding ,Immunoglobulin G ,Viruses ,biology.protein ,Interleukin-2 ,Antibody ,Protein Binding - Abstract
IgG responses are crucial in antiviral defence and instrumental for the serodiagnosis of infections. Fcγ receptors (FcγRs), which recognize the Fc-part of IgG, differ regarding their IgG binding affinity, IgG subclass preference, cellular expression profile and pathogen elimination mechanisms elicited upon activation. Assessing their activation in vitro is of fundamental importance, but technically difficult. Therefore, a novel assay for measuring antiviral IgG antibodies triggering activation of individual host Fcγ receptors was established. The assay comprises the co-cultivation of virus-infected target cells with immune IgG antibodies and mouse BW5147 hybridoma cells stably expressing chimeric FcγR–CD3ζ chain molecules consisting of the extracellular domain of human FcγRIIIA, FcγRIIA or FcγRI, respectively, fused to the transmembrane and intracellular domains of the mouse CD3ζ chain. Triggering of the chimeric FcγR receptors by immune complexes formed on the surface of IgG-opsonized virus-infected target cells resulted in FcγR activation leading to IL-2 secretion by BW5147 cells, which was quantified as a surrogate marker in an ELISA. Target cells infected with various human pathogenic viruses including herpes simplex virus type 1 (HSV-1), Epstein–Barr virus (EBV), human cytomegalovirus (HCMV), measles virus (MV), and respiratory syncytial virus (RSV) or displaying human immunodeficiency virus-1 (HIV-1) gp120 evoke dose-dependent IgG responses demonstrating the universal applicability of the assay. Taken together, a new reliable and simple tool for measuring antibodies triggering activation of Fcγ receptors was established. This assay will be instrumental for defining novel correlates of IgG immunity and the design of new therapeutic IgGs. UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiología
- Published
- 2013
36. Papel potencial de Aedes albopictus Skuse en la transmisión de virus dengue (DENV) en una zona de actividad piñera de Costa Rica
- Author
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Eugenia Corrales-Aguilar, Adriana Troyo, Rolando D. Moreira-Soto, Amanda Vicente-Santos, Olger Calderón-Arguedas, and Diana Rojas-Araya
- Subjects
Costa Rica ,Veterinary medicine ,Larva ,Aedes albopictus ,biology ,Virus transmission ,biology.organism_classification ,medicine.disease_cause ,medicine.disease ,Dengue fever ,616.921 Fiebre de dengue ,Limatus durhamii ,Dengue ,Culicidae ,flavivirus ,Aedes ,Infestation ,Biodiversity index ,medicine - Abstract
Objetivo. Evaluar, bajo una perspectiva ecológica, la presencia de Aedes albopictus y su infección natural por virus dengue (DENV) en una zona de actividad piñera de Costa Rica. Método: Se colectaron mosquitos adultos en galerías forestales colindantes con piñeras, viviendas en proximidad a cultivos (‹1 km) y viviendas en lejanía (1- 10 km). Se empleó el índice de Shannon-Wiener para estimar biodiversidad. La infestación larvaria se evaluó en plantas de piña y viviendas y se calcularon índices aédicos de viviendas (IV) y de contenedores (IC). La detección de DENV en adultos (cuerpos y cabezas) y en larvas de Ae. albopictus se efectuó mediante RT-PCR y secuenciación. Resultados. Se colectaron 1376 adultos en total: Ae. albopictus (5,81%), Anopheles apicimacula (5,01%), Culex coronator (11,55%), Cx. inflictus (6,1%), Cx. nigripalpus (48,11%), Cx. quinquefasciatus (23,34%) y Limatus durhamii (0,07%). El índice de biodiversidad fue mayor en galerías forestales. Ae. albopictus adultos fueron colectados principalmente en el área de piñeras (73/80), aunque sólo dos larvas en las plantas de piña. Los índices aédicos en proximidad (IV: 40,7%, IC: 26,9%) y en lejanía (IV: 51,7%, IC: 29,6%) no mostraron diferencias significativas (IV Z=0,56, p=0,58; IC Z=0,16, p=0,87). Se detectó DENV-2 y DENV-3 en 2/20 grupos de cabezas y DENV-1 en 2/74 grupos de larvas de Ae. albopictus. Discusión. Las galerías forestales próximas a cultivos de piña podrían considerarse “islas ecológicas” adecuadas para el refugio de Ae. albopictus. La presencia de DENV en adultos y larvas sugiere un papel activo de Ae. albopictus en la transmisión de virus en este ecosistema. Objective. To evaluate, under an ecological perspective, the presence of Aedes albopictus and the wild infection by dengue viruses (DENV) in an area of pineapple activity in Costa Rica.Materials and methods. Adult mosquitoes were collected in forest galleries limiting pineapple plantations, houses adjacent to plantations (
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