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Frontiers in microbiology2018; 9; 854; doi: 10.3389/fmicb.2018.00854

Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV.

Abstract: Hepatitis C virus (HCV) belongs to the 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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Publication Date: 2018-05-01 PubMed ID: 29765366PubMed Central: PMC5938362DOI: 10.3389/fmicb.2018.00854Google Scholar: Lookup
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Summary

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The research is focusing on the origin and adaptation of Hepatitis C virus (HCV) through an evolutionary analysis model. The scientists found that the common ancestor of present HCV genotypes existed at least 3000 years ago, mainly in Asia, and identified numerous sites in the virus’s genotypes that have been positively selected for drug resistance.

Overview of Hepatitis C Virus (HCV)

  • The study is based on Hepatitis C virus (HCV), a genetically diverse virus found in the Hepaciviruses genus. The virus has seven major genotypes, and within these genotypes, there are numerous subtypes.
  • While hepaciviruses are found in several domestic and wild mammals, they are most diverse in bats and rodents. Horses and donkeys (equine hepaciviruses or EHV) are known to carry the closest relatives to HCV.

Origins and Evolutionary Analysis of HCV

  • Using a new model of evolutionary research that incorporates selection, the researchers estimate the common ancestor of all current HCV genotypes existed around 3000 years ago. This contradicts previous research that dated the origin of HCV between 200 and 1000 years ago.
  • The oldest HCV genotypes are believed to be endemic to Asia, while EHV is thought to have originated around the year 1100.
  • Based on these timeframes, the researchers argue that HCV probably originated from a single event where the virus passed from animals to humans (zoonotic event). It then diversified within human populations.

HCV Drug Resistance and Genetic Variants

  • The researchers identified key sites within the primary HCV genotypes that have been positively selected, meaning these genetic variants have proven advantageous for the survival of the virus.
  • These positively selected sites are significantly enriched with genetic variants associated with drug resistance, making them important areas for ongoing research and development of HCV treatments.

HCV Cell Entry and Infection Specifics

  • HCV uses a number of cell-surface molecules to enter cells, but only two of these, CD81 and OCLN, determine the specific species that the virus can infect.
  • The evolutionary analysis found no indication of long-standing association between primates and hepaciviruses, and positive selection for CD81 was only observed in bats. No signs of selection were detected for OCLN in any mammalian species.
  • This aspect of the research provides insight into how the virus may have adapted over time and the specifics of its infection process.

This research thus provides a better understanding of the origins and evolution of HCV and contributes to a knowledge base that may ultimately assist in the development of more effective medications and treatments for hepatitis C.

Cite This Article

APA
Forni D, Cagliani R, Pontremoli C, Pozzoli U, Vertemara J, De Gioia L, Clerici M, Sironi M. (2018). Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV. Front Microbiol, 9, 854. https://doi.org/10.3389/fmicb.2018.00854

Publication

Frontiers in microbiology
ISSN: 1664-302X
NlmUniqueID: 101548977
Country: Switzerland
Language: English
Volume: 9
Pages: 854
PII: 854

Researcher Affiliations

Forni, Diego
  • Bioinformatics Laboratory, Scientific Institute IRCCS E.Medea, Bosisio Parini, Italy.
Cagliani, Rachele
  • Bioinformatics Laboratory, Scientific Institute IRCCS E.Medea, Bosisio Parini, Italy.
Pontremoli, Chiara
  • Bioinformatics Laboratory, Scientific Institute IRCCS E.Medea, Bosisio Parini, Italy.
Pozzoli, Uberto
  • Bioinformatics Laboratory, Scientific Institute IRCCS E.Medea, Bosisio Parini, Italy.
Vertemara, Jacopo
  • Department of Biotechnology and Biosciences, University of Milan-Bicocca, Milan, Italy.
De Gioia, Luca
  • Department of Biotechnology and Biosciences, University of Milan-Bicocca, Milan, Italy.
Clerici, Mario
  • Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
  • Don C. Gnocchi Foundation Onlus, IRCCS, Milan, Italy.
Sironi, Manuela
  • Bioinformatics Laboratory, Scientific Institute IRCCS E.Medea, Bosisio Parini, Italy.

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