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Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV

Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous, with seven major genotypes further divided into several recognized subtypes. HCV origin was previously dated in a range between ∼200 and 1000 years ago. Hepaciviruses have been identified in several domestic a...

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Autores principales: Forni, Diego, Cagliani, Rachele, Pontremoli, Chiara, Pozzoli, Uberto, Vertemara, Jacopo, De Gioia, Luca, Clerici, Mario, Sironi, Manuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938362/
https://www.ncbi.nlm.nih.gov/pubmed/29765366
http://dx.doi.org/10.3389/fmicb.2018.00854
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author Forni, Diego
Cagliani, Rachele
Pontremoli, Chiara
Pozzoli, Uberto
Vertemara, Jacopo
De Gioia, Luca
Clerici, Mario
Sironi, Manuela
author_facet Forni, Diego
Cagliani, Rachele
Pontremoli, Chiara
Pozzoli, Uberto
Vertemara, Jacopo
De Gioia, Luca
Clerici, Mario
Sironi, Manuela
author_sort Forni, Diego
collection PubMed
description Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous, with seven major genotypes further divided into several recognized subtypes. HCV origin was previously dated in a range between ∼200 and 1000 years ago. Hepaciviruses have been identified in several domestic and wild mammals, the largest viral diversity being observed in bats and rodents. The closest relatives of HCV were found in horses/donkeys (equine hepaciviruses, EHV). However, the origin of HCV as a human pathogen is still an unsolved puzzle. Using a selection-informed evolutionary model, we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago (CI: 3192–5221 years ago), with the oldest genotypes being endemic to Asia. EHV originated around 1100 CE (CI: 291–1640 CE). These time estimates exclude that EHV transmission was mainly sustained by widespread veterinary practices and suggest that HCV originated from a single zoonotic event with subsequent diversification in human populations. We also describe a number of biologically important sites in the major HCV genotypes that have been positively selected and indicate that drug resistance-associated variants are significantly enriched at positively selected sites. HCV exploits several cell-surface molecules for cell entry, but only two of these (CD81 and OCLN) determine the species-specificity of infection. Herein evolutionary analyses do not support a long-standing association between primates and hepaciviruses, and signals of positive selection at CD81 were only observed in Chiroptera. No evidence of selection was detected for OCLN in any mammalian order. These results shed light on the origin of HCV and provide a catalog of candidate genetic modulators of HCV phenotypic diversity.
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spelling pubmed-59383622018-05-14 Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV Forni, Diego Cagliani, Rachele Pontremoli, Chiara Pozzoli, Uberto Vertemara, Jacopo De Gioia, Luca Clerici, Mario Sironi, Manuela Front Microbiol Microbiology Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous, with seven major genotypes further divided into several recognized subtypes. HCV origin was previously dated in a range between ∼200 and 1000 years ago. Hepaciviruses have been identified in several domestic and wild mammals, the largest viral diversity being observed in bats and rodents. The closest relatives of HCV were found in horses/donkeys (equine hepaciviruses, EHV). However, the origin of HCV as a human pathogen is still an unsolved puzzle. Using a selection-informed evolutionary model, we show that the common ancestor of extant HCV genotypes existed at least 3000 years ago (CI: 3192–5221 years ago), with the oldest genotypes being endemic to Asia. EHV originated around 1100 CE (CI: 291–1640 CE). These time estimates exclude that EHV transmission was mainly sustained by widespread veterinary practices and suggest that HCV originated from a single zoonotic event with subsequent diversification in human populations. We also describe a number of biologically important sites in the major HCV genotypes that have been positively selected and indicate that drug resistance-associated variants are significantly enriched at positively selected sites. HCV exploits several cell-surface molecules for cell entry, but only two of these (CD81 and OCLN) determine the species-specificity of infection. Herein evolutionary analyses do not support a long-standing association between primates and hepaciviruses, and signals of positive selection at CD81 were only observed in Chiroptera. No evidence of selection was detected for OCLN in any mammalian order. These results shed light on the origin of HCV and provide a catalog of candidate genetic modulators of HCV phenotypic diversity. Frontiers Media S.A. 2018-05-01 /pmc/articles/PMC5938362/ /pubmed/29765366 http://dx.doi.org/10.3389/fmicb.2018.00854 Text en Copyright © 2018 Forni, Cagliani, Pontremoli, Pozzoli, Vertemara, De Gioia, Clerici and Sironi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Forni, Diego
Cagliani, Rachele
Pontremoli, Chiara
Pozzoli, Uberto
Vertemara, Jacopo
De Gioia, Luca
Clerici, Mario
Sironi, Manuela
Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV
title Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV
title_full Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV
title_fullStr Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV
title_full_unstemmed Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV
title_short Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV
title_sort evolutionary analysis provides insight into the origin and adaptation of hcv
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938362/
https://www.ncbi.nlm.nih.gov/pubmed/29765366
http://dx.doi.org/10.3389/fmicb.2018.00854
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