title: Viral evolution explains the associations among hepatitis C virus genotype, clinical outcomes, and human genetic variation.
abstract: Specific human polymorphisms, most commonly found in Central Africa, can predict the success of drug treatment against the hepatitis C virus (HCV), a significant and globally-distributed human pathogen. However, this association is only found for a subset of HCV genotypes. Despite receiving considerable attention in the medical and virological literature, no evolutionary explanation for this curious pattern has been put forward. Here we suggest that the 'drug treatment resistance' phenotype exhibited today by some HCV genotypes evolved hundreds to thousands of years ago in response to human genetic variation local to Central Africa: an adaptation that has since accrued a new function in the era of anti-viral drug treatment. This could represent one of the oldest known examples of viral exaptation at the population level.
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom. Electronic address: rebecca.rose@zoo.ox.ac.uk.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rose
authors.forename: Peter V
authors.initials: PV
authors.lastname: Markov
authors.forename: Tommy T
authors.initials: TT
authors.lastname: Lam
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Pybus
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000821:virology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012254:Ribavirin / Q000627:therapeutic use; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Co-evolution; Hepatitis C virus; IFNL3; Phylogeny; SNPs