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Viral evolution explains the associations among hepatitis C virus genotype, clinical outcomes, and human genetic

Rebecca Rose1, Peter V Markov, Tommy T Lam

  • 1Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom.

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
|October 22, 2013
PubMed

Insights

Human genetic variations in Central Africa influence hepatitis C virus (HCV) drug treatment success for specific genotypes. This study proposes an ancient evolutionary adaptation of HCV to human genetics, now impacting modern antiviral therapy effectiveness.

Area of Science:

  • Evolutionary biology
  • Virology
  • Human genetics

Background:

  • Hepatitis C virus (HCV) is a global pathogen.
  • Human genetic polymorphisms in Central Africa correlate with HCV drug treatment outcomes.
  • This correlation is genotype-specific, lacking an evolutionary explanation.

Purpose of the Study:

  • To propose an evolutionary explanation for the genotype-specific association between human polymorphisms and HCV drug treatment success.
  • To investigate the ancient origins of HCV's 'drug treatment resistance' phenotype.

Main Methods:

  • Comparative analysis of HCV genotypes and human genetic variation data.
  • Phylogenetic analysis to infer evolutionary history.
  • Literature review of virological and medical studies on HCV and human polymorphisms.

Main Results:

  • The 'drug treatment resistance' in some HCV genotypes likely evolved centuries to millennia ago.
  • This evolution was driven by adaptation to local Central African human genetic variation.
  • This ancient adaptation has been exapted for a new function in the era of antiviral drugs.

Conclusions:

  • HCV's interaction with human genetics has deep evolutionary roots.
  • Viral exaptation at the population level offers a novel perspective on pathogen adaptation.
  • Understanding this historical context is crucial for current and future HCV treatment strategies.

Keywords:
Co-evolutionHepatitis C virusIFNL3PhylogenySNPs

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