36 results on '"Muñoz-González, Sara"'
Search Results
2. Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence
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Hinojosa, Yoandry, primary, Liniger, Matthias, additional, García-Nicolás, Obdulio, additional, Gerber, Markus, additional, Rajaratnam, Anojen, additional, Muñoz-González, Sara, additional, Coronado, Liani, additional, Frías, María Teresa, additional, Perera, Carmen Laura, additional, Ganges, Llilianne, additional, and Ruggli, Nicolas, additional
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- 2024
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3. Novel poly-uridine insertion in the 3′UTR and E2 amino acid substitutions in a low virulent classical swine fever virus
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Coronado, Liani, Liniger, Matthias, Muñoz-González, Sara, Postel, Alexander, Pérez, Lester Josue, Pérez-Simó, Marta, Perera, Carmen Laura, Frías- Lepoureau, Maria Teresa, Rosell, Rosa, Grundhoff, Adam, Indenbirken, Daniela, Alawi, Malik, Fischer, Nicole, Becher, Paul, Ruggli, Nicolas, and Ganges, Llilianne
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- 2017
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4. Investigation of chronic and persistent classical swine fever infections under field conditions and their impact on vaccine efficacy
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Coronado, Liani, Bohórquez, Jose Alejandro, Muñoz-González, Sara, Perez, Lester Josue, Rosell, Rosa, Fonseca, Osvaldo, Delgado, Laiyen, Perera, Carmen Laura, Frías, Maria Teresa, and Ganges, Llilianne
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- 2019
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5. Removal of the E rns RNase Activity and of the 3′ Untranslated Region Polyuridine Insertion in a Low-Virulence Classical Swine Fever Virus Triggers a Cytokine Storm and Lethal Disease
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Wang, Miaomiao, primary, Bohórquez, José Alejandro, additional, Muñoz-González, Sara, additional, Gerber, Markus, additional, Alberch, Mònica, additional, Pérez-Simó, Marta, additional, Abad, Xavier, additional, Liniger, Matthias, additional, Ruggli, Nicolas, additional, and Ganges, Llilianne, additional
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- 2022
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6. Removal of the Erns RNase Activity and of the 39 Untranslated Region Polyuridine Insertion in a Low-Virulence Classical Swine Fever Virus Triggers a Cytokine Storm and Lethal Disease
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Wang, Miaomiao, Bohórquez, José Alejandro, Muñoz-González, Sara, Gerber, Markus, Alberch, Mònica, Pérez-Simó, Marta, Abad, Xavier, Liniger, Matthias, Ruggli, Nicolas, Ganges, Llilianne, Producció Animal, and Sanitat Animal
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In this study, we assessed the potential synergistic effect of the Erns RNase activity and the poly-U insertion in the 3′ untranslated region (UTR) of the low-virulence classical swine fever virus (CSFV) isolate Pinar de Rio (PdR) in innate and adaptive immunity regulation and its relationship with classical swine fever (CSF) pathogenesis in pigs. We knocked out the Erns RNase activity of PdR and replaced the long polyuridine sequence of the 3′ UTR with 5 uridines found typically at this position, resulting in a double mutant, vPdR-H30K-5U. This mutant induced severe CSF in 5-day-old piglets and 3-week-old pigs, with higher lethality in the newborn (89.5%) than in the older (33.3%) pigs. However, the viremia and viral excretion were surprisingly low, while the virus load was high in the tonsils. Only alpha interferon (IFN-α) and interleukin 12 (IL-12) were highly and consistently elevated in the two groups. Additionally, high IL-8 levels were found in the newborn but not in the older pigs. This points toward a role of these cytokines in the CSF outcome, with age-related differences. The disproportional activation of innate immunity might limit systemic viral spread from the tonsils and increase virus clearance, inducing strong cytokine-mediated symptoms. Infection with vPdR-H30K-5U resulted in poor neutralizing antibody responses compared with results obtained previously with the parent and RNase knockout PdR. This study shows for the first time the synergistic effect of the 3′ UTR and the Erns RNase function in regulating innate immunity against CSFV, favoring virus replication in target tissue and thus contributing to disease severity. IMPORTANCE CSF is one of the most relevant viral epizootic diseases of swine, with high economic and sanitary impact. Systematic stamping out of infected herds with and without vaccination has permitted regional virus eradication. However, the causative agent, CSFV, persists in certain areas of the world, leading to disease reemergence. Nowadays, low- and moderate-virulence strains that could induce unapparent CSF forms are prevalent, posing a challenge for disease eradication. Here, we show for the first time the synergistic role of lacking the Erns RNase activity and the 3′ UTR polyuridine insertion from a low-virulence CSFV isolate in innate immunity disproportional activation. This might limit systemic viral spread to the tonsils and increase virus clearance, inducing strong cytokine-mediated symptoms, thus contributing to disease severity. These results highlight the role played by the Erns RNase activity and the 3′ UTR in CSFV pathogenesis, providing new perspectives for novel diagnostic tools and vaccine strategies. info:eu-repo/semantics/publishedVersion
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- 2022
7. Abrogation of the RNase activity of Erns in a low virulence classical swine fever virus enhances the humoral immune response and reduces virulence, transmissibility, and persistence in pigs
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Wang, Miaomiao, primary, Bohórquez, José Alejandro, additional, Hinojosa, Yoandry, additional, Muñoz-González, Sara, additional, Gerber, Markus, additional, Coronado, Liani, additional, Perera, Carmen Laura, additional, Liniger, Matthias, additional, Ruggli, Nicolas, additional, and Ganges, Llilianne, additional
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- 2021
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8. The Inflammasome Components NLRP3 and ASC Act in Concert with IRGM To Rearrange the Golgi Apparatus during Hepatitis C Virus Infection
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Daussy, Coralie, Monard, Sarah, Guy, Coralie, Muñoz-González, Sara, Chazal, Maxime, Anthonsen, Marit, Jouvenet, Nolwenn, Henry, Thomas, Dreux, Marlène, Meurs, Eliane, Hansen, Marianne Doré, Hépacivirus et Immunité innée, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et Physiopathologie des Virus Oncogènes / Oncogenic Virus Epidemiology and Pathophysiology (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Signalisation antivirale - Virus sensing and signaling, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Département de Virologie - Department of Virology, Institut Pasteur [Paris], Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Trafic Vésiculaire, Réponse Innée et Virus – Vesicular trafficking, Innate response, Virus, mmunité innée et trafic vésiculaire - Vesicular trafficking, innate response and viruses (VIV), St. Olavs Hospital HF (St. Olav's University Hospital), This work was supported by grants from the Liaison Committee for Education, Research and Innovation in Central Norway to M.D.H., Agence Nationale pour la Recherche contre le SIDA et les Hépatites Virales (ANRS) to E.F.M., C.F.D., and M.D., and Agence Nationale pour la Recherche (ANR-JCJC) and LabEx Ecofect grant ANR-11-LABX-0048 to M.D., ANR-11-LABX-0048,ECOFECT,Dynamiques eco-évolutives des maladies infectieuses(2011), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), CHAZAL, MAXIME, Dynamiques eco-évolutives des maladies infectieuses - - ECOFECT2011 - ANR-11-LABX-0048 - LABX - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
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MESH: GTP-Binding Proteins ,Inflammasomes ,[SDV]Life Sciences [q-bio] ,Golgi Apparatus ,Apoptosis ,Golgi rearrangement ,Hepacivirus ,ASC ,MESH: Golgi Apparatus ,MESH: Inflammasomes ,NLRP3 ,GTP-Binding Proteins ,NLR Family, Pyrin Domain-Containing 3 Protein ,Humans ,MESH: Hepacivirus ,ZIKV ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,MESH: Hepatitis C ,MESH: Humans ,MESH: Apoptosis ,IRGM ,Hepatitis C ,Virus-Cell Interactions ,CARD Signaling Adaptor Proteins ,MESH: NLR Family, Pyrin Domain-Containing 3 Protein ,HCV ,MESH: CARD Signaling Adaptor Proteins ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology - Abstract
Numerous pathogens can affect cellular homeostasis and organelle dynamics. Hepatitis C virus (HCV) triggers Golgi fragmentation through the immunity-related GTPase M (IRGM), a resident Golgi protein, to enhance its lipid supply for replication., Hepatitis C virus (HCV) infection triggers Golgi fragmentation through the Golgi-resident protein immunity-related GTPase M (IRGM). Here, we report the roles of NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) and ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain [CARD]), two inflammasome components, in the initial events leading to this fragmentation. We show that ASC resides at the Golgi with IRGM at homeostasis. Upon infection, ASC dissociates from both IRGM and the Golgi and associates with HCV-induced NLRP3. NLRP3 silencing inhibits Golgi fragmentation. ASC silencing disrupts the Golgi structure in both control and infected cells and reduces the localization of IRGM at the Golgi. IRGM depletion in the ASC-silenced cells cannot totally restore the Golgi structure. These data highlight a role for ASC, upstream of the formation of the inflammasome, in regulating IRGM through its control on the Golgi. A similar mechanism occurs in response to nigericin treatment, but not in cells infected with another member of the Flaviviridae family, Zika virus (ZIKV). We propose a model for a newly ascribed function of the inflammasome components in Golgi structural remodeling during certain stimuli. IMPORTANCE Numerous pathogens can affect cellular homeostasis and organelle dynamics. Hepatitis C virus (HCV) triggers Golgi fragmentation through the immunity-related GTPase M (IRGM), a resident Golgi protein, to enhance its lipid supply for replication. Here, we reveal the role of the inflammasome components NLRP3 and ASC in this process, thus uncovering a new interplay between effectors of inflammation and viral infection or stress. We show that the inflammasome component ASC resides at the Golgi under homeostasis and associates with IRGM. Upon HCV infection, ASC is recruited to NLRP3 and dissociates from IRGM, causing Golgi fragmentation. Our results uncover that aside from their known function in the inflammation response, these host defense regulators also ensure the maintenance of intact intracellular structure in homeostasis, while their activation relieves factors leading to Golgi remodeling.
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- 2021
9. Adaptation to host cell environment during experimental evolution of Zika virus
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Grass, Vincent, primary, Hardy, Emilie, additional, Kobert, Kassian, additional, Talemi, Soheil Rastgou, additional, Décembre, Elodie, additional, Guy, Coralie, additional, Markov, Peter, additional, Kohl, Alain, additional, Paris, Mathilde, additional, Bockmann, Anja, additional, Muñoz-González, Sara, additional, Sherry, Lee, additional, Höfer, Thomas, additional, Boussau, Bastien, additional, and Dreux, Marlène, additional
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- 2021
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10. Adaptation to host cell environment during experimental evolution of Zika virus
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Grass, Vincent, primary, Hardy, Emilie, additional, Kobert, Kassian, additional, Talemi, Soheil Rastgou, additional, Décembre, Elodie, additional, Guy, Coralie, additional, Markov, Peter V., additional, Kohl, Alain, additional, Paris, Mathilde, additional, Böckmann, Anja, additional, Muñoz-González, Sara, additional, Sherry, Lee, additional, Höfer, Thomas, additional, Boussau, Bastien, additional, and Dreux, Marlène, additional
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- 2020
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11. The inflammasome components NLRP3 and ASC act in concert with IRGM to rearrange the Golgi during viral infections
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Daussy, Coralie F., primary, Monard, Sarah C., additional, Guy, Coralie, additional, Muñoz-González, Sara, additional, Chazal, Maxime, additional, Anthonsen, Marit W., additional, Jouvenet, Nolwenn, additional, Henry, Thomas, additional, Dreux, Marlène, additional, Meurs, Eliane F., additional, and Hansen, Marianne Doré, additional
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- 2020
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12. Foetal Immune Response Activation and High Replication Rate during Generation of Classical Swine Fever Congenital Infection
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Bohórquez, José Alejandro, primary, Muñoz-González, Sara, additional, Pérez-Simó, Marta, additional, Muñoz, Iván, additional, Rosell, Rosa, additional, Coronado, Liani, additional, Domingo, Mariano, additional, and Ganges, Llilianne, additional
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- 2020
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13. A Polyuridine Insertion in the 3′ Untranslated Region of Classical Swine Fever Virus Activates Immunity and Reduces Viral Virulence in Piglets
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Wang, Miaomiao, primary, Liniger, Matthias, additional, Muñoz-González, Sara, additional, Bohórquez, José Alejandro, additional, Hinojosa, Yoandry, additional, Gerber, Markus, additional, López-Soria, Sergio, additional, Rosell, Rosa, additional, Ruggli, Nicolas, additional, and Ganges, Llilianne, additional
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- 2020
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14. Abrogation of the RNase activity of Erns in a low virulence classical swine fever virus enhances the humoral immune response and reduces virulence, transmissibility, and persistence in pigs.
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Wang, Miaomiao, Bohórquez, José Alejandro, Hinojosa, Yoandry, Muñoz-González, Sara, Gerber, Markus, Coronado, Liani, Perera, Carmen Laura, Liniger, Matthias, Ruggli, Nicolas, and Ganges, Llilianne
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CLASSICAL swine fever virus ,CLASSICAL swine fever ,HUMORAL immunity ,IMMUNOREGULATION ,SWINE ,VIRAL transmission - Abstract
The prevalence of low virulence classical swine fever virus (CSFV) strains makes viral eradication difficult in endemic countries. However, the determinants for natural CSFV attenuation and persistence in the field remain unidentified. The aim of the present study was to assess the role of the RNase activity of CSFV E
rns in pathogenesis, immune response, persistent infection, and viral transmission in pigs. To this end, a functional cDNA clone pPdR-H30 K-36U with an Erns lacking RNase activity was constructed based on the low virulence CSFV field isolate Pinar de Rio (PdR). Eighteen 5-day-old piglets were infected with vPdR-H30 K-36U. Nine piglets were introduced as contacts. The vPdR-H30 K-36U virus was attenuated in piglets compared to the parental vPdR-36U. Only RNA traces were detected in sera and body secretions and no virus was isolated from tonsils, showing that RNase inactivation may reduce CSFV persistence and transmissibility. The vPdR-H30 K-36U mutant strongly activated the interferon-α (IFN-α) production in plasmacytoid dendritic cells, while in vivo, the IFN-α response was variable, from moderate to undetectable depending on the animal. This suggests a role of the CSFV Erns RNase activity in the regulation of innate immune responses. Infection with vPdR-H30 K-36U resulted in higher antibody levels against the E2 and Erns glycoproteins and in enhanced neutralizing antibody responses when compared with vPdR-36U. These results pave the way toward a better understanding of viral attenuation mechanisms of CSFV in pigs. In addition, they provide novel insights relevant for the development of DIVA vaccines in combination with diagnostic assays for efficient CSF control. [ABSTRACT FROM AUTHOR]- Published
- 2021
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15. Do humans spread zoonotic enteric bacteria in Antarctica?
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Cerdà-Cuéllar, Marta, primary, Moré, Elisabet, additional, Ayats, Teresa, additional, Aguilera, Mònica, additional, Muñoz-González, Sara, additional, Antilles, Noelia, additional, Ryan, Peter G., additional, and González-Solís, Jacob, additional
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- 2019
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16. Atypical porcine pestivirus in wild boar (Sus scrofa ), Spain
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Colom-Cadena, Andreu, primary, Ganges, Llilianne, additional, Muñoz-González, Sara, additional, Castillo-Contreras, Raquel, additional, Bohórquez, José Alejandro, additional, Rosell, Rosa, additional, Segalés, Joaquim, additional, Marco, Ignasi, additional, and Cabezon, Oscar, additional
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- 2018
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17. Abrogation of the RNase activity of Ernsin a low virulence classical swine fever virus enhances the humoral immune response and reduces virulence, transmissibility, and persistence in pigs
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Wang, Miaomiao, Bohórquez, José Alejandro, Hinojosa, Yoandry, Muñoz-González, Sara, Gerber, Markus, Coronado, Liani, Perera, Carmen Laura, Liniger, Matthias, Ruggli, Nicolas, and Ganges, Llilianne
- Abstract
ABSTRACTThe prevalence of low virulence classical swine fever virus (CSFV) strains makes viral eradication difficult in endemic countries. However, the determinants for natural CSFV attenuation and persistence in the field remain unidentified. The aim of the present study was to assess the role of the RNase activity of CSFV Ernsin pathogenesis, immune response, persistent infection, and viral transmission in pigs. To this end, a functional cDNA clone pPdR-H30K-36U with an Ernslacking RNase activity was constructed based on the low virulence CSFV field isolate Pinar de Rio (PdR). Eighteen 5-day-old piglets were infected with vPdR-H30K-36U. Nine piglets were introduced as contacts. The vPdR-H30K-36U virus was attenuated in piglets compared to the parental vPdR-36U. Only RNA traces were detected in sera and body secretions and no virus was isolated from tonsils, showing that RNase inactivation may reduce CSFV persistence and transmissibility. The vPdR-H30K-36U mutant strongly activated the interferon-α (IFN-α) production in plasmacytoid dendritic cells, while in vivo, the IFN-α response was variable, from moderate to undetectable depending on the animal. This suggests a role of the CSFV ErnsRNase activity in the regulation of innate immune responses. Infection with vPdR-H30K-36U resulted in higher antibody levels against the E2 and Ernsglycoproteins and in enhanced neutralizing antibody responses when compared with vPdR-36U. These results pave the way toward a better understanding of viral attenuation mechanisms of CSFV in pigs. In addition, they provide novel insights relevant for the development of DIVA vaccines in combination with diagnostic assays for efficient CSF control.
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- 2021
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18. Propuestas de mejora de promoción al empleo para egresados universitarios.Una visión desde la investigación y la experiencia docente
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Sánchez Robert, María José, Muñoz González, Sara, Romero Coronado, Juan, Sánchez Robert, María José, Muñoz González, Sara, and Romero Coronado, Juan
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- Graduate students--Employment
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- 2018
19. A bivalent dendrimeric peptide bearing a T-cell epitope from foot-and-mouth disease virus protein 3A improves humoral response against classical swine fever virus
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Bohórquez, José Alejandro, Defaus, Sira, Muñoz-González, Sara, Perez-Simó, Marta, Rosell, Rosa, Fraile, Lorenzo, Sobrino, Francisco, Andreu, David, and Ganges, Llilianne
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- 2017
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20. El derecho comparado en la docencia y la investigación.
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Muñoz González, Sara, Muñoz González, Mª Carmen, Marchal Escalona, Nuria, Muñoz González, Sara, Muñoz González, Mª Carmen, and Marchal Escalona, Nuria
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- Law--Philosophy, Law--Language
- Abstract
El Derecho, en cuanto a ciencia social, no puede, al igual que ocurre con la historia, la economía, la teoría política o la sociología, ser estudiado exclusivamente desde una perspectiva puramente nacional. Deviene preciso e imprescindible conocer las diferencias y similitudes entre distintas familias y sistemas jurídicos, permitiendo que el Derecho evolucione, proponiendo para tal efecto comparaciones, recepciones, trasplantes o fusiones, propicia el análisis de figuras jurídicas utilizadas en otros países y su posible adaptación a otro sistema. No existe una definición del Derecho comparado que pueda englobar todas sus funciones y fijar una finalidad concreta, y la razón es simple, que es un método comparativo al servicio de todas las ramas jurídicas (Derecho penal, Derecho internacional privado, Derecho mercantil, Derecho constitucional, Derecho laboral, etc).Ahora bien, el método comparado requiere de unos presupuestos básicos para ser comprendido y aplicado. Es preciso comprender y analizar la noción misma y sus posibilidades metodológicas en el ámbito de la investigación y de la docencia. Precisamente, la presente obra nace con la vocación de darlos a conocer optando por una perspectiva práctica. El Derecho, como saber o como ciencia, es fundamentalmente práctico, por su propia razón de ser. Son los problemas y los conflictos entre partes, los que justifican la realidad jurídica. Y deber ser la pericia en la solución de esos problemas prácticos la razón de ser primordial de la enseñanza jurídica. Ciertamente, solo un conocimiento profundo de la teoría y su aplicación práctica hace al buen jurista.Este libro es fruto de la innegable utilidad y de las bondades que el método comparado presenta.El objetivo es difundir en la Universidad española las virtudes del método comparado. Y es que, desgraciadamente, el Derecho comparado no cuenta con un espacio propio en las Facultades de Derecho de las Universidades españolas. La formación de los alumnos en el ámbito de la metodología jurídica comparada es, pues, cuando menos escasa. Sin embargo, y he ahí la paradoja, rara es la rama jurídica o de ciencias sociales en la que no se elaboren trabajos de investigación, trabajos fin de Grado o fin de Máster con contenidos de Derecho comparado. Con la presente obra tratamos, por tanto, de satisfacer la necesidad imperiosa de preparar al alumno para un mercado laboral como lo es el actual, globalizado y cambiante.
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- 2017
21. Immunopathogenesis of postnatal persistent infection generated by classical swine fever virus and its implication in the superinfection exclusion phenomenon
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Muñoz González, Sara, Domingo, Mariano, Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals, and Domingo Álvarez, Mariano
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Virus superinfection exclusion ,Interferencia viral ,Persistencia vírica ,Viral persistence ,Virus de la PPC ,CSFV ,Persistència vírica ,Interferència viral ,Ciències de la Salut - Abstract
La peste porcina clásica (PPC) es una enfermedad viral altamente contagiosa de cerdos domésticos y salvajes, incluida en la lista de enfermedades de declaración obligatoria a la Organización Mundial de Sanidad Animal. El agente causal, el virus PPC (VPPC), pertenece al género Pestivirus, familia Flaviviridae. A pesar de los grandes esfuerzos dirigidos a controlar y erradicar la PPC, continúa siendo una de las enfermedades más importantes para la sanidad animal y la industria porcina en todo el mundo. La circulación y la importancia intrínseca de cepas de VPPC de baja y moderada virulencia en las regiones endémicas ha sido objeto de discusión en los últimos años. Varios trabajos han demostrado el papel de cepas de baja virulencia en el nacimiento de lechones persistentemente infectados (PI) con el VPPC. No obstante, los mecanismos involucrados en este tipo de infecciones por VPPC no son bien conocidos, y los estudios existentes datan de hace 40 años. Por otro lado, la posible generación de persistencia viral después de la infección postnatal con VPPC era todavía una cuestión a resolver. Esta tesis demuestra la capacidad de cepas de VPPC de baja y moderada virulencia de inducir persistencia vírica de forma postnatal en cerdo doméstico y salvaje. Para ello, cerditos recién nacidos fueron inoculados de forma intranasal con el VPPC. Durante seis semanas, estos lechones permanecieron aparentemente sanos, a pesar de no generar respuesta inmunológica celular ni humoral específica para VPPC. Se demostró viremia permanente y alta carga de virus en todas las muestras de tejido, secreciones y excreciones de los animales persistentemente infectados (PI), hasta el fin del estudio. Además, se demostró la ineficacia de la vacunación de cerdos PI, de seis semanas de edad, los cuales no generaron respuesta de IFN de tipo I ni de tipo II, ni de anticuerpos durante 21 días tras la vacunación con una vacuna viva atenuada de VPPC (la C-strain). La falta de detección del ARN vacunal mediante RT-qPCR específica en sangre, excreciones y tejidos, incluyendo la tonsila, sugirió la ausencia de replicación del virus vacunal en los animales PI y un posible fenómeno de interferencia viral. Finalmente, jabalíes de seis semanas de vida con infección persistente de VPPC (primera infección) fueron inoculados con una cepa de alta virulencia de VPPC (segunda infección o superinfección). Los jabalíes PI no desarrollaron signos clínicos y mostraron alta carga del virus primario, causante de la persistencia, en todas las muestras analizadas. Por el contrario, el virus secundario no fue detectado ni por RT-qPCR ni por secuenciación, demostrando así el fenómeno de exclusión de la superinfección (ESI). La ausencia de una respuesta de IFN de tipo I y II y de anticuerpos respaldó los resultados previos de los estudios de esta tesis. Estos hallazgos demostraron por primera vez la capacidad del VPPC para inducir ESI in vivo, en cerdos con infección persistente. El fenómeno ESI probablemente explicaría la falta de respuesta de los animales con infección persistente después de la vacunación con la vacuna viva atenuada. Considerando la existencia de cepas de virulencia baja a moderada y su capacidad para producir formas de infección persistente, los resultados aquí presentados pueden tener potenciales repercusiones epidemiológicas, especialmente en el contexto endémico. Es importante destacar que los animales persistentemente infectados pasarían desapercibidos bajo control serológico, dada la ausencia de respuesta de anticuerpos específicos. Esta tesis doctoral ha contribuido a la comprensión de la patogénesis producida por el VPPC, que depende no sólo de la virulencia de la cepa sino también de la interacción virus-huésped, y abre nuevas líneas de investigación para comprender los mecanismos subyacentes que conducen a la generación de inmunotolerancia y persistencia del VPPC., Classical swine fever (CSF) is a highly contagious viral disease of domestic and wild pigs, included in the list of diseases notifiable to the World Organisation for Animal Health. The causative agent, CSF virus (CSFV), belongs to the Pestivirus genus, Flaviviridae family. Over the last century, great efforts have been directed towards the control and eradication of CSF, which today remains one of the most important diseases for animal health and in the pig industry worldwide. The circulation and intrinsic importance of low and moderate virulence strains in the endemic regions has been extensively described. Also, it has been shown the role of these type of viral strains in the generation of “the pregnant carrier sow syndrome” and persistent infection of piglets after trans-placental transmission. However, the mechanisms involved in this form of CSFV infections are not well known, and the existing studies date over 40 years ago. By contrast, the possible generation of viral persistence after postnatal infection of pigs is still a question to resolve. Against this background, this thesis has demonstrated the capacity of low and moderate virulence CSFV strains to produce postnatal persistent infection early after birth. To this end, newborn piglets were inoculated intranasally with CSFV. During six weeks, these piglets remained apparently healthy, although they were not able to generate detectable CSFV specific humoral nor cellular immune responses, maintaining high virus load in blood, organs and body secretions and excretions. In addition, it has been demonstrated the ineffectiveness of vaccination of six-week-old PI pigs, which were unable to elicit a detectable innate immune response, in terms of IFN type-I production, as well as acquired immune responses (i.e. IFN type-II and antibodies) following vaccination with a CSFV live attenuated vaccine (C-strain). The RNA of the vaccine could not be detected by a specific RT-qPCR in any of the samples analysed after vaccination, including the tonsil, suggesting a superinfection exclusion (SIE) phenomenon between the persistently infecting virus (primary infection) and the CSFV vaccine strain (secondary infection). Finally, six-week-old wild boars with CSFV persistent infection (first infection) were inoculated with a CSFV strain of high virulence (second infection or superinfection). PI wild boars did not develop clinical signs and showed a high load of the primary virus, causing persistence, in all samples analysed. In contrast, the secondary virus was not detected by either RT-qPCR or sequence analyses, thus demonstrating the phenomenon of superinfection exclusion (SIE). The lack of innate and acquired immune responses supported the previous studies from this thesis. In addition, in vitro assays with the PBMCs isolated ex vivo from persistently infected animals, a well-known target for the CSFV viral replication, further corroborated the CSFV SIE phenomenon. These findings demonstrated for the first time the ability of CSFV to induce SIE in vivo, in swine with persistent infection. The SIE phenomenon would likely explain the unresponsiveness of animals with persistent infection after vaccination with the live attenuated vaccine. Considering the existence of CSFV strains of low and moderate virulence and their ability to produce persistent infection forms, the results showed here may have potential epidemiological repercussions, especially in the endemic context. Importantly, persistently infected animals would remain unnoticed under serological control, given the absence of specific antibody response. This doctoral thesis has contributed to the understanding of the pathogenesis of CSFV infection, which depends not only on the virulence of the strain but also on the virus-host interaction, and opens new lines of research to understand the immunological bases and of viral pathogenesis for the generation of immunotolerance and persistence, hitherto unknown.
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- 2017
22. El poder de la comunicación. Claves de la comunicación estratégica en los espacios jurídico y político
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Muñoz González, Sara, Ortega Pérez, Nieves, Serrano Escribano, Selina, Triguero Martínez, Luis Ángel (eds.), Muñoz González, Sara, Ortega Pérez, Nieves, Serrano Escribano, Selina, and Triguero Martínez, Luis Ángel (eds.)
- Subjects
- Communication--Political aspects, Communication in law, Communication
- Abstract
El poder de la comunicación. Claves de la comunicación estratégica en los espacios jurídico y político, destaca de modo práctico y profesional la decidida influencia que en la arena jurídica y política tienen la comunicación y sus estrategias como una de las competencias profesionales más importantes y valoradas. El perfil interdisciplinar de este libro parte de la consideración de que la comunicación se ha convertido en un elemento clave para las instituciones democráticas y la sociedad civil. En las últimas décadas, asistimos a una demanda mayor de participación de ésta en los distintos ámbitos. Las líneas entre los actores públicos y privados, y las distintas áreas de acción, se han difuminado. Los medios de comunicación se han transformado y los escenarios de debate han pasado a formar parte de una suerte de repositorio público donde las estrategias de la comunicación resultan imprescindibles para comprenderlo y participar del mismo. Esta obra está dirigida tanto a aquellos que quieran reflexionar sobre las claves de los nuevos modelos comunicativos en los espacios jurídico y político, como a los profesionales que requieran potenciar esta habilidad. Este trabajo actúa como guía de recursos formativos e instrumento de apoyo práctico orientado a la vida profesional.
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- 2016
23. Corrigendum to “Efficacy of E2 glycoprotein fused to porcine CD154 as a novel chimeric subunit vaccine to prevent classical swine fever virus vertical transmission in pregnant sows”
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Muñoz-González, Sara, primary, Sordo, Yusmel, additional, Pérez-Simó, Marta, additional, Suarez, Marisela, additional, Canturri, Albert, additional, Rodriguez, Maria Pilar, additional, Frías-Lepoureau, María Teresa, additional, Domingo, Mariano, additional, Estrada, Mario Pablo, additional, and Ganges, Llilianne, additional
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- 2018
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24. African swine fever virus infection in Classical swine fever subclinically infected wild boars
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Cabezón, Oscar, primary, Muñoz-González, Sara, additional, Colom-Cadena, Andreu, additional, Pérez-Simó, Marta, additional, Rosell, Rosa, additional, Lavín, Santiago, additional, Marco, Ignasi, additional, Fraile, Lorenzo, additional, de la Riva, Paloma Martínez, additional, Rodríguez, Fernando, additional, Domínguez, Javier, additional, and Ganges, Llilianne, additional
- Published
- 2017
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25. Efficacy of E2 glycoprotein fused to porcine CD154 as a novel chimeric subunit vaccine to prevent classical swine fever virus vertical transmission in pregnant sows
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Muñoz-González, Sara, primary, Sordo, Yusmel, additional, Pérez-Simó, Marta, additional, Suárez, Marisela, additional, Canturri, Albert, additional, Rodriguez, Maria Pilar, additional, Frías-Lepoureau, María Teresa, additional, Domingo, Mariano, additional, Estrada, Mario Pablo, additional, and Ganges, Llilianne, additional
- Published
- 2017
- Full Text
- View/download PDF
26. Classical Swine Fever Virus vs. Classical Swine Fever Virus: The Superinfection Exclusion Phenomenon in Experimentally Infected Wild Boar
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Muñoz-González, Sara, primary, Pérez-Simó, Marta, additional, Colom-Cadena, Andreu, additional, Cabezón, Oscar, additional, Bohórquez, José Alejandro, additional, Rosell, Rosa, additional, Pérez, Lester Josué, additional, Marco, Ignasi, additional, Lavín, Santiago, additional, Domingo, Mariano, additional, and Ganges, Llilianne, additional
- Published
- 2016
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27. Las rutinas en infantil como herramienta para trabajar las habilidades sociales
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Muñoz González, Sara and Mielgo Figueroa, Lucía
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Tesis y disertaciones académicas - Abstract
Proyecto Fin de Grado-Universidad Pontificia de Salamanca, Facultad de Ciencias Humanas y Sociales, 2012, Las rutinas infantiles se fundamentan en la vida cotidiana como fuente de aprendizaje diario y continuo. La vida cotidiana es el soporte del aprendizaje de las acciones cotidianas y de las rutinas, inevitables para el bienestar y referencia de los niños/as. La vida cotidiana ha de estar estructurada espacial y temporalmente ya que el entorno resulta ser, en definitiva, el medio en el que los escolares desarrollan su actividad, la cual es esencialmente lúdica. Lo que se pretende al organizar de esta manera su día a día es que el alumno desarrolle habilidades y estrategias necesarias y que sea capaz de regular su propia actividad. Se muestra aquí un programa que bien podría utilizarse en cualquier aula de infantil.
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- 2012
28. Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs
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Muñoz-González, Sara, primary, Perez-Simó, Marta, additional, Muñoz, Marta, additional, Bohorquez, José Alejandro, additional, Rosell, Rosa, additional, Summerfield, Artur, additional, Domingo, Mariano, additional, Ruggli, Nicolas, additional, and Ganges, Llilianne, additional
- Published
- 2015
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29. Postnatal Persistent Infection with Classical Swine Fever Virus and Its Immunological Implications
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Muñoz-González, Sara, primary, Ruggli, Nicolas, additional, Rosell, Rosa, additional, Pérez, Lester Josué, additional, Frías-Leuporeau, Maria Teresa, additional, Fraile, Lorenzo, additional, Montoya, Maria, additional, Cordoba, Lorena, additional, Domingo, Mariano, additional, Ehrensperger, Felix, additional, Summerfield, Artur, additional, and Ganges, Llilianne, additional
- Published
- 2015
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30. Removal of the Erns RNase Activity and of the 39 Untranslated Region Polyuridine Insertion in a Low-Virulence Classical Swine Fever Virus Triggers a Cytokine Storm and Lethal Disease.
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Miaomiao Wang, Alejandro Bohórquez, José, Muñoz-González, Sara, Gerber, Markus, Alberch, Mònica, Pérez-Simó, Marta, Abad, Xavier, Liniger, Matthias, Ruggli, Nicolas, and Ganges, Llilianne
- Subjects
- *
CLASSICAL swine fever virus , *CLASSICAL swine fever , *CYTOKINE release syndrome , *ANTIVIRAL agents , *IMMUNOREGULATION , *NATURAL immunity , *VIRAL transmission - Abstract
In this study, we assessed the potential synergistic effect of the Erns RNase activity and the poly-U insertion in the 39 untranslated region (UTR) of the low-virulence classical swine fever virus (CSFV) isolate Pinar de Rio (PdR) in innate and adaptive immunity regulation and its relationship with classical swine fever (CSF) pathogenesis in pigs. We knocked out the Erns RNase activity of PdR and replaced the long polyuridine sequence of the 39 UTR with 5 uridines found typically at this position, resulting in a double mutant, vPdR-H30K-5U. This mutant induced severe CSF in 5-day-old piglets and 3-week-old pigs, with higher lethality in the newborn (89.5%) than in the older (33.3%) pigs. However, the viremia and viral excretion were surprisingly low, while the virus load was high in the tonsils. Only alpha interferon (IFN-a) and interleukin 12 (IL-12) were highly and consistently elevated in the two groups. Additionally, high IL-8 levels were found in the newborn but not in the older pigs. This points toward a role of these cytokines in the CSF outcome, with age-related differences. The disproportional activation of innate immunity might limit systemic viral spread from the tonsils and increase virus clearance, inducing strong cytokine-mediated symptoms. Infection with vPdR-H30K-5U resulted in poor neutralizing antibody responses compared with results obtained previously with the parent and RNase knockout PdR. This study shows for the first time the synergistic effect of the 39 UTR and the Erns RNase function in regulating innate immunity against CSFV, favoring virus replication in target tissue and thus contributing to disease severity. IMPORTANCE CSF is one of the most relevant viral epizootic diseases of swine, with high economic and sanitary impact. Systematic stamping out of infected herds with and without vaccination has permitted regional virus eradication. However, the causative agent, CSFV, persists in certain areas of the world, leading to disease reemergence. Nowadays, low- and moderate-virulence strains that could induce unapparent CSF forms are prevalent, posing a challenge for disease eradication. Here, we show for the first time the synergistic role of lacking the Erns RNase activity and the 39 UTR polyuridine insertion from a low-virulence CSFV isolate in innate immunity disproportional activation. This might limit systemic viral spread to the tonsils and increase virus clearance, inducing strong cytokine-mediated symptoms, thus contributing to disease severity. These results highlight the role played by the Erns RNase activity and the 39 UTR in CSFV pathogenesis, providing new perspectives for novel diagnostic tools and vaccine strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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31. Identification of an Immunosuppressive Cell Population during Classical Swine Fever Virus Infection and Its Role in Viral Persistence in the Host.
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Bohorquez, Jose Alejandro, Muñoz-González, Sara, Pérez-Simó, Marta, Revilla, Concepción, Domínguez, Javier, and Ganges, Llilianne
- Subjects
- *
CLASSICAL swine fever virus , *CLASSICAL swine fever , *CELL populations , *VIRUS diseases , *BONE marrow cells , *INTERFERON gamma - Abstract
Classical swine fever virus (CSFV) remains a highly important pathogen, causing major losses in the swine industry. Persistent infection is highly relevant for CSFV maintenance in the field; however, this form of infection is not fully understood. An increase in the granulocyte population has been detected in CSFV persistently infected animals. The aim of this work was to evaluate the possible immunosuppressive role of these cells in CSFV persistent infection. The phenotype of peripheral blood and bone marrow cells from persistently infected and naïve animals was evaluated by flow cytometry, and the capacity of specific cell subsets to reduce the interferon gamma (IFN-γ) response against unspecific and specific antigen was determined using co-culture assays. The frequency of granulocytic cells was increased in cells from CSFV persistently infected pigs and they showed a phenotype similar to immunosuppressive cell populations found in persistent infection in humans. These cells from persistently infected animals were able to reduce the IFN-γ response against unspecific and specific antigen. Our results suggest that immature immunosuppressive cell populations play a role in CSFV persistent infection in swine. The information obtained by studying the role of myeloid derived suppressor cells (MDSC) during CSFV persistent infection may extrapolate to other viral persistent infections in mammals. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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32. Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs
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Muñoz, Marta, Muñoz-González, Sara, Ruggli, Nicolas, Ganges, Llilianne, Bohorquez, José Alejandro, Rosell, Rosa, Domingo, Mariano, Summerfield, Artur, and Perez-Simó, Marta
- Subjects
630 Agriculture ,3. Good health - Abstract
Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.
33. A Polyuridine Insertion in the 3' Untranslated Region of Classical Swine Fever Virus Activates Immunity and Reduces Viral Virulence in Piglets.
- Author
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Miaomiao Wang, Liniger, Matthias, Muñoz-González, Sara, Alejandro Bohórquez, José, Hinojosa, Yoandry, Gerber, Markus, López-Soria, Sergio, Rosell, Rosa, Ruggli, Nicolas, and Ganges, Llilianne
- Subjects
- *
CLASSICAL swine fever virus , *CLASSICAL swine fever , *PIGLETS , *HUMORAL immunity , *INTERFERON alpha - Abstract
Low-virulence classical swine fever virus (CSFV) strains make CSF eradication particularly difficult. Few data are available on the molecular determinants of CSFV virulence. The aim of the present study was to assess a possible role for CSFV virulence of a unique, uninterrupted 36-uridine (poly-U) sequence found in the 3' untranslated region (3' UTR) of the low-virulence CSFV isolate Pinar de Rio (PdR). To this end, a pair of cDNA-derived viruses based on the PdR backbone were generated, one carrying the long poly-U insertion in the 3= UTR (vPdR-36U) and the other harboring the standard 5 uridines at this position (vPdR-5U). Two groups of 20 5-day-old piglets were infected with vPdR-36U and vPdR-5U. Ten contact piglets were added to each group. Disease progression, virus replication, and immune responses were monitored for 5 weeks. The vPdR-5U virus was significantly more virulent than the vPdR-36U virus, with more severe disease, higher mortality, and significantly higher viral loads in serum and body secretions, despite similar replication characteristics in cell culture. The two viruses were transmitted to all contact piglets. Ninety percent of the piglets infected with vPdR-36U seroconverted, while only one vPdR-5U-infected piglet developed antibodies. The vPdR-5U-infected piglets showed only transient alpha interferon (IFN-α) responses in serum after 1 week of infection, while the vPdR-36U-infected piglets showed sustained IFN-α levels during the first 2 weeks. Taken together, these data show that the 3' UTR poly-U insertion acquired by the PdR isolate reduces viral virulence and activates the innate and humoral immune responses without affecting viral transmission. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
34. Adaptation to host cell environment during experimental evolution of Zika virus
- Author
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Sara Munoz-Gonzalez, Coralie Guy, Elodie Décembre, Peter Markov, Bastien Boussau, Alain Kohl, Marlène Dreux, Mathilde Paris, Thomas Höfer, Kassian Kobert, Vincent Grass, Soheil Rastgou Talemi, Emilie Hardy, Anja Böckmann, Lee Sherry, Trafic Vésiculaire, Réponse Innée et Virus – Vesicular trafficking, Innate response, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Luxembourg Institute of Health (LIH), MRC - University of Glasgow Centre for Virus Research, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle de Lyon (IGFL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Le Cocon, Département PEGASE [LBBE] (PEGASE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Virus, mmunité innée et trafic vésiculaire - Vesicular trafficking, innate response and viruses (VIV), Grass, Vincent [0000-0001-7710-4789], Talemi, Soheil Rastgou [0000-0002-9999-2403], Décembre, Elodie [0000-0001-6891-6320], Kohl, Alain [0000-0002-1523-9458], Muñoz-González, Sara [0000-0002-7846-7001], Sherry, Lee [0000-0002-4367-772X], Höfer, Thomas [0000-0003-3560-8780], Boussau, Bastien [0000-0003-0776-4460], Dreux, Marlène [0000-0002-6607-4796], and Apollo - University of Cambridge Repository
- Subjects
Infectivity ,Experimental evolution ,Zika Virus Infection ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,Medicine (miscellaneous) ,Zika Virus ,Biology ,biology.organism_classification ,Phenotype ,Virology ,Antiviral Agents ,Virus ,General Biochemistry, Genetics and Molecular Biology ,Zika virus ,Toll-Like Receptor 3 ,Viral replication ,Interferon ,Viral evolution ,medicine ,Humans ,Interferons ,General Agricultural and Biological Sciences ,medicine.drug - Abstract
Zika virus (ZIKV) infection can cause developmental and neurological defects and represents a threat for human health. Type I/III interferon responses control ZIKV infection and pathological processes, yet the virus has evolved various mechanisms to defeat these host responses. Here, we established a pipeline to delineate at high-resolution the genetic evolution of ZIKV in a controlled host cell environment. We uncovered that serially passaged ZIKV acquired increased infectivity, defined as the probability for one virus to initiate infection, and simultaneously developed a resistance to TLR3-induced restriction. We built a mathematical model that suggests that the increased infectivity is due to a reduced time-lag between infection and viral replication. We found that this adaptation is cell-type specific, suggesting that different cell environments may drive viral evolution along different routes. Deep-sequencing of ZIKV quasi-species pinpointed mutations whose increased frequencies temporally coincide with the acquisition of the adapted phenotype. We functionally validated a point-mutation in ZIKV envelope (E) protein recapitulating the adapted phenotype. Its positioning on the E structure suggests a putative function in protein refolding/stability. Altogether, our results uncovered ZIKV adaptations to the cell environment leading to an accelerated replication onset coupled with resistance to TLR3-induced antiviral response. Our work provides insights into viral escape mechanisms and interactions with host cell and can serve as a framework to study other viruses.
- Published
- 2020
35. Abrogation of the RNase activity of E rns in a low virulence classical swine fever virus enhances the humoral immune response and reduces virulence, transmissibility, and persistence in pigs.
- Author
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Wang M, Bohórquez JA, Hinojosa Y, Muñoz-González S, Gerber M, Coronado L, Perera CL, Liniger M, Ruggli N, and Ganges L
- Subjects
- Animals, Persistent Infection, Swine, Virulence, Classical Swine Fever immunology, Classical Swine Fever transmission, Classical Swine Fever Virus enzymology, Immunity, Humoral, Ribonucleases genetics
- Abstract
The prevalence of low virulence classical swine fever virus (CSFV) strains makes viral eradication difficult in endemic countries. However, the determinants for natural CSFV attenuation and persistence in the field remain unidentified. The aim of the present study was to assess the role of the RNase activity of CSFV E
rns in pathogenesis, immune response, persistent infection, and viral transmission in pigs. To this end, a functional cDNA clone pPdR-H30 K-36U with an Erns lacking RNase activity was constructed based on the low virulence CSFV field isolate Pinar de Rio (PdR). Eighteen 5-day-old piglets were infected with vPdR-H30 K-36U. Nine piglets were introduced as contacts. The vPdR-H30 K-36U virus was attenuated in piglets compared to the parental vPdR-36U. Only RNA traces were detected in sera and body secretions and no virus was isolated from tonsils, showing that RNase inactivation may reduce CSFV persistence and transmissibility. The vPdR-H30 K-36U mutant strongly activated the interferon-α (IFN-α) production in plasmacytoid dendritic cells, while in vivo , the IFN-α response was variable, from moderate to undetectable depending on the animal. This suggests a role of the CSFV Erns RNase activity in the regulation of innate immune responses. Infection with vPdR-H30 K-36U resulted in higher antibody levels against the E2 and Erns glycoproteins and in enhanced neutralizing antibody responses when compared with vPdR-36U. These results pave the way toward a better understanding of viral attenuation mechanisms of CSFV in pigs. In addition, they provide novel insights relevant for the development of DIVA vaccines in combination with diagnostic assays for efficient CSF control.- Published
- 2021
- Full Text
- View/download PDF
36. The Inflammasome Components NLRP3 and ASC Act in Concert with IRGM To Rearrange the Golgi Apparatus during Hepatitis C Virus Infection.
- Author
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Daussy CF, Monard SC, Guy C, Muñoz-González S, Chazal M, Anthonsen MW, Jouvenet N, Henry T, Dreux M, Meurs EF, and Hansen MD
- Subjects
- Apoptosis, CARD Signaling Adaptor Proteins genetics, GTP-Binding Proteins genetics, Golgi Apparatus virology, Hepatitis C metabolism, Hepatitis C pathology, Humans, NLR Family, Pyrin Domain-Containing 3 Protein genetics, CARD Signaling Adaptor Proteins metabolism, GTP-Binding Proteins metabolism, Golgi Apparatus physiology, Hepacivirus isolation & purification, Hepatitis C virology, Inflammasomes metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism
- Abstract
Hepatitis C virus (HCV) infection triggers Golgi fragmentation through the Golgi-resident protein immunity-related GTPase M (IRGM). Here, we report the roles of NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) and ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain [CARD]), two inflammasome components, in the initial events leading to this fragmentation. We show that ASC resides at the Golgi with IRGM at homeostasis. Upon infection, ASC dissociates from both IRGM and the Golgi and associates with HCV-induced NLRP3. NLRP3 silencing inhibits Golgi fragmentation. ASC silencing disrupts the Golgi structure in both control and infected cells and reduces the localization of IRGM at the Golgi. IRGM depletion in the ASC-silenced cells cannot totally restore the Golgi structure. These data highlight a role for ASC, upstream of the formation of the inflammasome, in regulating IRGM through its control on the Golgi. A similar mechanism occurs in response to nigericin treatment, but not in cells infected with another member of the Flaviviridae family, Zika virus (ZIKV). We propose a model for a newly ascribed function of the inflammasome components in Golgi structural remodeling during certain stimuli. IMPORTANCE Numerous pathogens can affect cellular homeostasis and organelle dynamics. Hepatitis C virus (HCV) triggers Golgi fragmentation through the immunity-related GTPase M (IRGM), a resident Golgi protein, to enhance its lipid supply for replication. Here, we reveal the role of the inflammasome components NLRP3 and ASC in this process, thus uncovering a new interplay between effectors of inflammation and viral infection or stress. We show that the inflammasome component ASC resides at the Golgi under homeostasis and associates with IRGM. Upon HCV infection, ASC is recruited to NLRP3 and dissociates from IRGM, causing Golgi fragmentation. Our results uncover that aside from their known function in the inflammation response, these host defense regulators also ensure the maintenance of intact intracellular structure in homeostasis, while their activation relieves factors leading to Golgi remodeling., (Copyright © 2021 Daussy et al.)
- Published
- 2021
- Full Text
- View/download PDF
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