Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

eLife

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[1] Blizard Institute, Queen Mary University, London, United Kingdom;Department of Statistics, University of Oxford, Oxford, United Kingdom;Institute of Liver Studies, King's College Hospital, London, United Kingdom;MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Glasgow, United Kingdom;National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom;Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, United Kingdom;Wellcome Centre Human Genetics, University of Oxford, Oxford, United Kingdom;Wellcome Centre Human Genetics, University of Oxford, Oxford, United Kingdom;Laboratoire MIVEGEC (UMR CNRS 5290, IRD, UM), Montpellier, France;

关键词: hepatitis C virus;    genome-to-genome analysis;    host-pathogen interactions;    interferon lambda 4;    innate immunity;    Human;    Virus;   

DOI  :  10.7554/eLife.42463

来源: publisher

【 摘 要 】

10.7554/eLife.42463.001Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability is affected by the adaptive immune response but the contribution of other host factors is unclear. Here, we examined the role played by interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays a crucial role in spontaneous clearance or establishment of chronicity following acute infection. We performed viral genome-wide association studies using human and viral data from 485 patients of white ancestry infected with HCV genotype 3a. We demonstrate that combinations of host genetic variants, which determine IFN-λ4 protein production and activity, influence amino acid variation across the viral polyprotein - not restricted to specific viral proteins or HLA restricted epitopes - and modulate viral load. We also observed an association with viral di-nucleotide proportions. These results support a direct role for IFN-λ4 in exerting selective pressure across the viral genome, possibly by a novel mechanism.

【 授权许可】

CC BY