24 results on '"Muñoz-González, Sara"'
Search Results
2. 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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3. Evolutionary-Related High- and Low-Virulent Classical Swine Fever Virus Isolates Reveal Viral Determinants of Virulence.
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Hinojosa, Yoandry, Liniger, Matthias, García-Nicolás, Obdulio, Gerber, Markus, Rajaratnam, Anojen, Muñoz-González, Sara, Coronado, Liani, Frías, María Teresa, Perera, Carmen Laura, Ganges, Llilianne, and Ruggli, Nicolas
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CLASSICAL swine fever ,CLASSICAL swine fever virus ,REVERSE genetics ,RECOMBINANT viruses ,CYTOSKELETAL proteins - Abstract
Classical swine fever (CSF) has been eradicated from Western and Central Europe but remains endemic in parts of Central and South America, Asia, and the Caribbean. CSF virus (CSFV) has been endemic in Cuba since 1993, most likely following an escape of the highly virulent Margarita/1958 strain. In recent years, chronic and persistent infections with low-virulent CSFV have been observed. Amino acid substitutions located in immunodominant epitopes of the envelope glycoprotein E2 of the attenuated isolates were attributed to positive selection due to suboptimal vaccination and control. To obtain a complete picture of the mutations involved in attenuation, we applied forward and reverse genetics using the evolutionary-related low-virulent CSFV/Pinar del Rio (CSF1058)/2010 (PdR) and highly virulent Margarita/1958 isolates. Sequence comparison of the two viruses recovered from experimental infections in pigs revealed 40 amino acid differences. Interestingly, the amino acid substitutions clustered in E2 and the NS5A and NS5B proteins. A long poly-uridine sequence was identified previously in the 3′ untranslated region (UTR) of PdR. We constructed functional cDNA clones of the PdR and Margarita strains and generated eight recombinant viruses by introducing single or multiple gene fragments from Margarita into the PdR backbone. All chimeric viruses had comparable replication characteristics in porcine monocyte-derived macrophages. Recombinant PdR viruses carrying either E2 or NS5A/NS5B of Margarita, with 36 or 5 uridines in the 3′UTR, remained low virulent in 3-month-old pigs. The combination of these elements recovered the high-virulent Margarita phenotype. These results show that CSFV evolution towards attenuated variants in the field involved mutations in both structural and non-structural proteins and the UTRs, which act synergistically to determine virulence. [ABSTRACT FROM AUTHOR]
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- 2024
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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. 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.
- Published
- 2021
6. 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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7. 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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8. 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, Sordo, Yusmel, Pérez-Simó, Marta, Suarez, Marisela, Canturri, Albert, Rodriguez, Maria Pilar, Frías-Lepoureau, María Teresa, Domingo, Mariano, Estrada, Mario Pablo, and Ganges, Llilianne
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CLASSICAL swine fever vaccines , *SOWS , *GLYCOPROTEINS , *DISEASES - Abstract
Here we evaluated the effect of double vaccination with a novel subunit marker vaccine candidate based in the CSFV E2 glycoprotein fused to the porcine CD154 to prevent CSFV vertical transmission. A lentivirus-based gene delivery system was used to obtain a stable recombinant HEK 293 cell line for the expression of E2 fused to porcine CD154 molecule. Six pregnant sows were distributed in two groups and at 64 days of gestation animals numbered 1–4 (group 1) were vaccinated via intramuscular inoculation with 50 μg of E2-CD154 subunit vaccine. Animals from group 2 (numbered 5 and 6, control animals) were injected with PBS. Seventeen days later sows from group 1 were boosted with the same vaccine dose. Twenty-seven days after the first immunization, the sows were challenged with a virulent CSFV Margarita strain and clinical signs were registered. Samples were collected during the experiment and at necropsy to evaluate immune response and virological protection. Between 14 and 18 days after challenge, the sows were euthanized, the foetuses were obtained and samples of sera and tissues were collected. E2-CD154 vaccinated animals remained clinically healthy until the end of the study; also, no adverse reaction was shown after vaccination. An effective boost effect in the neutralizing antibody response after the second immunization and viral challenge was observed and supports the virological protection detected in these animals after vaccination. Protection against CSFV vertical transmission was found in the 100% of serums samples from foetus of vaccinated sows. Only two out of 208 samples (0.96%) were positive with Ct value about 36 corresponding to one tonsil and one thymus, which may be non-infective viral particles. Besides, its DIVA potential and protection from vertical transmission, the novel CSFV E2 bound to CD154 subunit vaccine, is a promising alternative to the live-attenuated vaccine for developing countries. [ABSTRACT FROM AUTHOR]
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- 2018
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9. African swine fever virus infection in Classical swine fever subclinically infected wild boars.
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Cabezón, Oscar, Muñoz-González, Sara, Colom-Cadena, Andreu, Pérez-Simó, Marta, Rosell, Rosa, Lavín, Santiago, Marco, Ignasi, Fraile, Lorenzo, Martínez de la Riva, Paloma, Rodríguez, Fernando, Domínguez, Javier, and Ganges, Llilianne
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AFRICAN swine fever , *VIRUS diseases , *ARBOVIRUS diseases in animals , *VIRUS diseases in swine , *VIREMIA , *PESTIVIRUS diseases - Abstract
Background: Recently moderate-virulence classical swine fever virus (CSFV) strains have been proven capable of generating postnatal persistent infection (PI), defined by the maintenance of viremia and the inability to generate CSFV-specific immune responses in animals. These animals also showed a type I interferon blockade in the absence of clinical signs. In this study, we assessed the infection generated in 7-week-old CSFV PI wild boars after infection with the African swine fever virus (ASFV). The wild boars were divided in two groups and were infected with ASFV. Group A comprised boars who were CSFV PI in a subclinical form and Group B comprised pestivirus-free wild boars. Some relevant parameters related to CSFV replication and the immune response of CSFV PI animals were studied. Additionally, serum soluble factors such as IFN-α, TNF-α, IL-6, IL-10, IFN-γ and sCD163 were analysed before and after ASFV infection to assess their role in disease progression. Results: After ASFV infection, only the CSFV PI wild boars showed progressive acute haemorrhagic disease; however, the survival rates following ASFV infection was similar in both experimental groups. Notwithstanding, the CSFV RNA load of CSFV PI animals remained unaltered over the study; likewise, the ASFV DNA load detected after infection was similar between groups. Interestingly, systemic type I FN-α and IL-10 levels in sera were almost undetectable in CSFV PI animals, yet detectable in Group B, while detectable levels of IFN-γ were found in both groups. Finally, the flow cytometry analysis showed an increase in myelomonocytic cells (CD172a+) and a decrease in CD4+ T cells in the PBMCs from CSFV PI animals after ASFV infection. Conclusions: Our results showed that the immune response plays a role in the progression of disease in CSFV subclinically infected wild boars after ASFV infection, and the immune response comprised the systemic type I interferon blockade. ASFV does not produce any interference with CSFV replication, or vice versa. ASFV infection could be a trigger factor for the disease progression in CSFV PI animals, as their survival after ASFV was similar to that of the pestivirus-free ASFV-infected group. This fact suggests a high resistance in CSFV PI animals even against a virus like ASFV; this may mean that there are relevant implications for CSF control in endemic countries. The diagnosis of ASFV and CSFV co-infection in endemic countries cannot be ruled out and need to be studied in greater depth. [ABSTRACT FROM AUTHOR]
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- 2017
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10. 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, Sordo, Yusmel, Pérez-Simó, Marta, Suárez, Marisela, Canturri, Albert, Rodriguez, Maria Pilar, Frías-Lepoureau, María Teresa, Domingo, Mariano, Estrada, Mario Pablo, and Ganges, Llilianne
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DRUG efficacy , *GLYCOPROTEINS , *CLASSICAL swine fever virus , *VIRAL vaccines , *VERTICAL transmission (Communicable diseases) , *CD antigens - Abstract
Here we evaluated the effect of double vaccination with a novel subunit marker vaccine candidate based in the CSFV E2 glycoprotein fused to the porcine CD154 to prevent CSFV vertical transmission. A lentivirus-based gene delivery system was used to obtain a stable recombinant HEK 293 cell line for the expression of E2 fused to porcine CD154 molecule. Six pregnant sows were distributed in two groups and at 64 days of gestation animals numbered 1–4 (group 1) were vaccinated via intramuscular inoculation with 50 μg of E2-CD154 subunit vaccine. Animals from group 2 (numbered 5 and 6, control animals) were injected with PBS. Seventeen days later sows from group 1 were boosted with the same vaccine dose. Twenty-seven days after the first immunization, the sows were challenged with a virulent CSFV Margarita strain and clinical signs were registered. Samples were collected during the experiment and at necropsy to evaluate immune response and virological protection. Between 14 and 18 days after challenge, the sows were euthanized, the foetuses were obtained and samples of sera and tissues were collected. E2-CD154 vaccinated animals remained clinically healthy until the end of the study; also, no adverse reaction was shown after vaccination. An effective boost effect in the neutralizing antibody response after the second immunization and viral challenge was observed and support the virological protection detected in these animals after vaccination. Protection against CSFV vertical transmission was found in the 100% of serums samples from foetus of vaccinated sows. Only two out of 208 samples (0.96%) were positive with Ct value about 36 corresponding to one tonsil and one thymus, which may be non-infective viral particles. Besides, its DIVA potential and protection from vertical transmission, the novel CSFV E2 bound to CD154 subunit vaccine, is a promising alternative to the live-attenuated vaccine for developing countries. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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11. Atypical porcine pestivirus in wild boar (Sus scrofa), Spain.
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Colom-Cadena, Andreu, Ganges, Llilianne, Muñoz-González, Sara, Castillo-Contreras, Raquel, Alejandro Bohórquez, José, Rosell, Rosa, Segalés, Joaquim, Marco, Ignasi, and Cabezon, Oscar
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PESTIVIRUS diseases ,WILD boar ,VIRUS diseases ,VIRUS diseases in swine ,VETERINARY medicine - Published
- 2018
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12. 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, Pérez-Simó, Marta, Colom-Cadena, Andreu, Cabezón, Oscar, Bohórquez, José Alejandro, Rosell, Rosa, Pérez, Lester Josué, Marco, Ignasi, Lavín, Santiago, Domingo, Mariano, and Ganges, Llilianne
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SUPERINFECTION , *WILD boar , *VETERINARY virology , *VIRUS virulence , *POLYMERASE chain reaction , *CROSS reactions (Immunology) , *DISEASES ,CLASSICAL swine fever diagnosis - Abstract
Two groups with three wild boars each were used: Group A (animals 1 to 3) served as the control, and Group B (animals 4 to 6) was postnatally persistently infected with the Cat01 strain of CSFV (primary virus). The animals, six weeks old and clinically healthy, were inoculated with the virulent strain Margarita (secondary virus). For exclusive detection of the Margarita strain, a specific qRT-PCR assay was designed, which proved not to have cross-reactivity with the Cat01 strain. The wild boars persistently infected with CSFV were protected from superinfection by the virulent CSFV Margarita strain, as evidenced by the absence of clinical signs and the absence of Margarita RNA detection in serum, swabs and tissue samples. Additionally, in PBMCs, a well-known target for CSFV viral replication, only the primary infecting virus RNA (Cat01 strain) could be detected, even after the isolation in ST cells, demonstrating SIE at the tissue level in vivo. Furthermore, the data analysis of the Margarita qRT-PCR, by means of calculated ΔCt values, supported that PBMCs from persistently infected animals were substantially protected from superinfection after in vitro inoculation with the Margarita virus strain, while this virus was able to infect naive PBMCs efficiently. In parallel, IFN-α values were undetectable in the sera from animals in Group B after inoculation with the CSFV Margarita strain. Furthermore, these animals were unable to elicit adaptive humoral (no E2-specific or neutralising antibodies) or cellular immune responses (in terms of IFN-γ-producing cells) after inoculation with the second virus. Finally, a sequence analysis could not detect CSFV Margarita RNA in the samples tested from Group B. Our results suggested that the SIE phenomenon might be involved in the evolution and phylogeny of the virus, as well as in CSFV control by vaccination. To the best of our knowledge, this study was one of the first showing efficient suppression of superinfection in animals, especially in the absence of IFN-α, which might be associated with the lack of innate immune mechanisms. [ABSTRACT FROM AUTHOR]
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- 2016
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13. Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs.
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Muñoz-González, Sara, Perez-Simó, Marta, Muñoz, Marta, Bohorquez, José Alejandro, Rosell, Rosa, Summerfield, Artur, Domingo, Mariano, Ruggli, Nicolas, and Ganges, Llilianne
- 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. [ABSTRACT FROM AUTHOR]
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- 2015
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14. Postnatal Persistent Infection with Classical Swine Fever Virus and Its Immunological Implications.
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Muñoz-González, Sara, Ruggli, Nicolas, Rosell, Rosa, Pérez, Lester Josué, Frías-Leuporeau, Maria Teresa, Fraile, Lorenzo, Montoya, Maria, Cordoba, Lorena, Domingo, Mariano, Ehrensperger, Felix, Summerfield, Artur, and Ganges, Llilianne
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POSTNATAL care , *IMMUNOLOGY , *VIRAL transmission , *MICROBIAL virulence , *PUBLIC health ,CLASSICAL swine fever diagnosis - Abstract
It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed. In addition to the epidemiological and economic significance of persistent CSFV infection, this model could be useful for understanding the mechanisms of viral persistence. [ABSTRACT FROM AUTHOR]
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- 2015
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15. 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
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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]
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- 2022
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16. Foetal Immune Response Activation and High Replication Rate during Generation of Classical Swine Fever Congenital Infection.
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Bohórquez, José Alejandro, Muñoz-González, Sara, Pérez-Simó, Marta, Muñoz, Iván, Rosell, Rosa, Coronado, Liani, Domingo, Mariano, and Ganges, Llilianne
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CLASSICAL swine fever virus ,CLASSICAL swine fever ,IMMUNE response - Abstract
Classical swine fever virus (CSFV) induces trans-placental transmission and congenital viral persistence; however, the available information is not updated. Three groups of sows were infected at mid-gestation with either a high, moderate or low virulence CSFV strains. Foetuses from sows infected with high or low virulence strain were obtained before delivery and piglets from sows infected with the moderate virulence strain were studied for 32 days after birth. The low virulence strain generated lower CSFV RNA load and the lowest proportion of trans-placental transmission. Severe lesions and mummifications were observed in foetuses infected with the high virulence strain. Sows infected with the moderately virulence strain showed stillbirths and mummifications, one of them delivered live piglets, all CSFV persistently infected. Efficient trans-placental transmission was detected in sows infected with the high and moderate virulence strain. The trans-placental transmission occurred before the onset of antibody response, which started at 14 days after infection in these sows and was influenced by replication efficacy of the infecting strain. Fast and solid immunity after sow vaccination is required for prevention of congenital viral persistence. An increase in the CD8+ T-cell subset and IFN-alpha response was found in viremic foetuses, or in those that showed higher viral replication in tissue, showing the CSFV recognition capacity by the foetal immune system after trans-placental infection. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
17. Identification of an Immunosuppressive Cell Population during Classical Swine Fever Virus Infection and Its Role in Viral Persistence in the Host.
- Author
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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
- Full Text
- View/download PDF
18. Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs
- Author
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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.
19. 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
20. Do humans spread zoonotic enteric bacteria in Antarctica?
- Author
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Cerdà-Cuéllar, Marta, Moré, Elisabet, Ayats, Teresa, Aguilera, Mònica, Muñoz-González, Sara, Antilles, Noelia, Ryan, Peter G., and González-Solís, Jacob
- Abstract
Abstract Reports of enteric bacteria in Antarctic wildlife have suggested its spread from people to seabirds and seals, but evidence is scarce and fragmentary. We investigated the occurrence of zoonotic enteric bacteria in seabirds across the Antarctic and subantarctic region; for comparison purposes, in addition to seabirds, poultry in a subantarctic island was also sampled. Three findings suggest reverse zoonosis from humans to seabirds: the detection of a zoonotic Salmonella serovar (ser. Enteritidis) and Campylobacter species (e.g. C. jejuni), typical of human infections; the resistance of C. lari isolates to ciprofloxacin and enrofloxacin, antibiotics commonly used in human and veterinary medicine; and most importantly, the presence of C. jejuni genotypes mostly found in humans and domestic animals but rarely or never found in wild birds so far. We also show further spread of zoonotic agents among Antarctic wildlife is facilitated by substantial connectivity among populations of opportunistic seabirds, notably skuas (Stercorarius). Our results highlight the need for even stricter biosecurity measures to limit human impacts in Antarctica. Graphical abstract Unlabelled Image Highlights • Three findings suggest that reverse zoonosis occurs in the Southern Ocean. • Scavenging species carry Salmonella ser. Enteritidis and C. jejuni genotypes of anthropogenic origin. • Genetic similarities among C. lari isolates suggest substantial connectivity across Southern Ocean localities. • Stricter biosecurity measures are needed to limit human impacts in Antarctica. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
21. 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.
- Author
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Wang M, Bohórquez JA, Muñoz-González S, Gerber M, Alberch M, Pérez-Simó M, Abad X, Liniger M, Ruggli N, and Ganges L
- Subjects
- 3' Untranslated Regions genetics, Adaptive Immunity genetics, Animals, Cytokines, Immunity, Innate genetics, Interferon-alpha immunology, Interleukin-12 immunology, Ribonucleases genetics, Ribonucleases metabolism, Swine, Viral Vaccines, Virulence genetics, Classical Swine Fever immunology, Classical Swine Fever pathology, Classical Swine Fever virology, Classical Swine Fever Virus enzymology, Classical Swine Fever Virus genetics, Classical Swine Fever Virus immunology, Classical Swine Fever Virus pathogenicity, Cytokine Release Syndrome genetics, Cytokine Release Syndrome immunology, Cytokine Release Syndrome virology
- Abstract
In this study, we assessed the potential synergistic effect of the E
rns 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-H30 K-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-H30 K-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.- Published
- 2022
- Full Text
- View/download PDF
22. 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
23. 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
24. 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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Wang M, Liniger M, Muñoz-González S, Bohórquez JA, Hinojosa Y, Gerber M, López-Soria S, Rosell R, Ruggli N, and Ganges L
- Subjects
- Animals, Humans, Interferon-alpha immunology, Swine, 3' Untranslated Regions immunology, Classical Swine Fever genetics, Classical Swine Fever immunology, Classical Swine Fever pathology, Classical Swine Fever Virus genetics, Classical Swine Fever Virus immunology, Classical Swine Fever Virus pathogenicity, Mutagenesis, Insertional, Poly U genetics, Poly U immunology, RNA, Viral genetics, RNA, Viral immunology
- 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. IMPORTANCE Classical swine fever (CSF), a highly contagious viral disease of pigs, is still endemic in some countries of Asia and Central and South America. Considering that the 3' untranslated region (3' UTR) plays an important role in flavivirus replication, the present study showed for the first time that a long polyuridine sequence acquired in the 3' UTR by an endemic CSFV isolate can activate immunity, control viral replication, and modulate disease in piglets. Our findings provide new avenues for the development of novel vaccines against infections with CSF virus and other flaviviruses. Knowledge of molecular virulence determinants is also relevant for future development of rapid and efficient diagnostic tools for the prediction of the virulence of field isolates and for efficient CSF control., (Copyright © 2020 Wang et al.)
- Published
- 2020
- Full Text
- View/download PDF
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