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Convergent Evolution of Escape from Hepaciviral Antagonism in Primates

The ability to mount an interferon response on sensing viral infection is a critical component of mammalian innate immunity. Several viruses directly antagonize viral sensing pathways to block activation of the host immune response. Here, we show that recurrent viral antagonism has shaped the evolut...

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Autores principales: Patel, Maulik R., Loo, Yueh-Ming, Horner, Stacy M., Gale, Michael, Malik, Harmit S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302847/
https://www.ncbi.nlm.nih.gov/pubmed/22427742
http://dx.doi.org/10.1371/journal.pbio.1001282
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author Patel, Maulik R.
Loo, Yueh-Ming
Horner, Stacy M.
Gale, Michael
Malik, Harmit S.
author_facet Patel, Maulik R.
Loo, Yueh-Ming
Horner, Stacy M.
Gale, Michael
Malik, Harmit S.
author_sort Patel, Maulik R.
collection PubMed
description The ability to mount an interferon response on sensing viral infection is a critical component of mammalian innate immunity. Several viruses directly antagonize viral sensing pathways to block activation of the host immune response. Here, we show that recurrent viral antagonism has shaped the evolution of the host protein MAVS—a crucial component of the viral-sensing pathway in primates. From sequencing and phylogenetic analyses of MAVS from 21 simian primates, we found that MAVS has evolved under strong positive selection. We focused on how this positive selection has shaped MAVS' susceptibility to Hepatitis C virus (HCV). We functionally tested MAVS proteins from diverse primate species for their ability to resist antagonism by HCV, which uses its protease NS3/4A to cleave human MAVS. We found that MAVS from multiple primates are resistant to inhibition by the HCV protease. This resistance maps to single changes within the protease cleavage site in MAVS, which protect MAVS from getting cleaved by the HCV protease. Remarkably, most of these changes have been independently acquired at a single residue 506 that evolved under positive selection. We show that “escape” mutations lower affinity of the NS3 protease for MAVS and allow it to better restrict HCV replication. We further show that NS3 proteases from all other primate hepaciviruses, including the highly divergent GBV-A and GBV-C viruses, are functionally similar to HCV. We conclude that convergent evolution at residue 506 in multiple primates has resulted in escape from antagonism by hepaciviruses. Our study provides a model whereby insights into the ancient history of viral infections in primates can be gained using extant host and virus genes. Our analyses also provide a means by which primates might clear infections by extant hepaciviruses like HCV.
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spelling pubmed-33028472012-03-16 Convergent Evolution of Escape from Hepaciviral Antagonism in Primates Patel, Maulik R. Loo, Yueh-Ming Horner, Stacy M. Gale, Michael Malik, Harmit S. PLoS Biol Research Article The ability to mount an interferon response on sensing viral infection is a critical component of mammalian innate immunity. Several viruses directly antagonize viral sensing pathways to block activation of the host immune response. Here, we show that recurrent viral antagonism has shaped the evolution of the host protein MAVS—a crucial component of the viral-sensing pathway in primates. From sequencing and phylogenetic analyses of MAVS from 21 simian primates, we found that MAVS has evolved under strong positive selection. We focused on how this positive selection has shaped MAVS' susceptibility to Hepatitis C virus (HCV). We functionally tested MAVS proteins from diverse primate species for their ability to resist antagonism by HCV, which uses its protease NS3/4A to cleave human MAVS. We found that MAVS from multiple primates are resistant to inhibition by the HCV protease. This resistance maps to single changes within the protease cleavage site in MAVS, which protect MAVS from getting cleaved by the HCV protease. Remarkably, most of these changes have been independently acquired at a single residue 506 that evolved under positive selection. We show that “escape” mutations lower affinity of the NS3 protease for MAVS and allow it to better restrict HCV replication. We further show that NS3 proteases from all other primate hepaciviruses, including the highly divergent GBV-A and GBV-C viruses, are functionally similar to HCV. We conclude that convergent evolution at residue 506 in multiple primates has resulted in escape from antagonism by hepaciviruses. Our study provides a model whereby insights into the ancient history of viral infections in primates can be gained using extant host and virus genes. Our analyses also provide a means by which primates might clear infections by extant hepaciviruses like HCV. Public Library of Science 2012-03-13 /pmc/articles/PMC3302847/ /pubmed/22427742 http://dx.doi.org/10.1371/journal.pbio.1001282 Text en Patel et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Patel, Maulik R.
Loo, Yueh-Ming
Horner, Stacy M.
Gale, Michael
Malik, Harmit S.
Convergent Evolution of Escape from Hepaciviral Antagonism in Primates
title Convergent Evolution of Escape from Hepaciviral Antagonism in Primates
title_full Convergent Evolution of Escape from Hepaciviral Antagonism in Primates
title_fullStr Convergent Evolution of Escape from Hepaciviral Antagonism in Primates
title_full_unstemmed Convergent Evolution of Escape from Hepaciviral Antagonism in Primates
title_short Convergent Evolution of Escape from Hepaciviral Antagonism in Primates
title_sort convergent evolution of escape from hepaciviral antagonism in primates
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3302847/
https://www.ncbi.nlm.nih.gov/pubmed/22427742
http://dx.doi.org/10.1371/journal.pbio.1001282
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