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Innate and adaptive immunity shape circulating HCV strains

Nature Genetics volume 49, pages 657–658 (2017)Cite this article

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An unbiased genome-to-genome analysis in chronic hepatitis C virus (HCV) infection confirms the innate and adaptive arms of the immune system as drivers of viral evolution. Viral adaptation has a critical role in the interaction between host and pathogen and has important clinical implications for infection outcome.

RNA viruses such as HCV and HIV have a high mutation rate, resulting in the occurrence of random mutations in the viral genome that can confer a selective advantage to the virus within the host environment. Strains harboring these adaptive mutations are likely to increase in frequency within the host to become the dominant circulating strain. Identifying these adaptations, referred to as 'footprints', has been difficult and requires large genomic data sets. Recently, reductions in sequencing costs coupled with improvements in allelic imputation have increased the feasibility of studies that examine the effect of host genes on the evolution of pathogens1. On page 666 of this issue, Chris Spencer, Eleanor Barnes and colleagues2 use a genome-to-genome approach sampling host and viral diversity in a cohort of subjects with chronic, predominantly genotype 3 HCV infection to identify, without a priori information, two regions in the human genome associated with variation in the virus: the interferon lambda (IFN-λ) region and the major histocompatibility complex (MHC) region containing the human leukocyte antigen (HLA) genes. Genes in these regions are involved in the innate and adaptive arms of the immune system and have previously been independently implicated in HCV infection and/or treatment outcome with IFN-based regimens3.

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Figure 1: The host antiviral immune response is a major driver of HCV evolution.

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Authors and Affiliations

  1. the Division of Infectious Disease, Department of Medicine, Silvana Gaudieri is in the School of Human Sciences, University of Western Australia, Perth, Western Australia, Australia, Vanderbilt University Medical Center, Nashville, Tennessee, USA, and the Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia.,

    Silvana Gaudieri

  2. Michaela Lucas is at the Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia, the School of Medicine and Pharmacology, Harry Perkins Institute, University of Western Australia, Perth, Western Australia, Australia, and the School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia, Australia.,

    Michaela Lucas

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  1. Silvana Gaudieri
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Correspondence to Silvana Gaudieri.

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The authors declare no competing financial interests.

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Gaudieri, S., Lucas, M. Innate and adaptive immunity shape circulating HCV strains. Nat Genet 49, 657–658 (2017). https://doi.org/10.1038/ng.3856

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