Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV

Frontiers in Microbiology
Diego ForniManuela Sironi

Abstract

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 selec...Continue Reading

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Citations

Aug 21, 2019·Frontiers in Public Health·Kristof TheysGuy Baele
Sep 10, 2020·The Journal of Biological Chemistry·Machaela PalorJoe Grove
Jan 18, 2021·The Journal of Biological Chemistry·Machaela PalorJoe Grove

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Software Mentioned

r8s
Patchdock
aBS
PyMOL Molecular Graphics System
RDP4
GUIDANCE
LigPrep
Mixed Effects Model of Evolution ( MEME )
Genetic Algorithm Recombination Detection ( GARD )
PRANK

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