Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus

M. Azim Ansari; Vincent Pedergnana; Camilla L. C. Ip; Andrea Magri; Annette Von Delft; David Bonsall; Nimisha Chaturvedi; Istvan Bartha; David Smith; George Nicholson; Gilean McVean; Amy Trebes; Paolo Piazza; Jacques Fellay; Graham Cooke; Graham R. Foster; Emma Hudson; John McLauchlan; Peter Simmonds; Rory Bowden; Paul Klenerman; Eleanor Barnes; Chris C. A. Spencer; STOP-HCV Consortium

doi:10.1038/ng.3835

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Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus

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Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus

M. Azim Ansari, Vincent Pedergnana, Camilla L. C. Ip, Andrea Magri, Annette Von Delft, David Bonsall, Nimisha Chaturvedi, Istvan Bartha, David Smith, George Nicholson, …

Nature genetics, Vol.49(5), pp.666-673

01/05/2017

DOI: https://doi.org/10.1038/ng.3835

PMID: 28394351

Résumé

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. Here we use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals who were chronically infected with HCV, predominantly genotype 3. We show that both alleles of genes encoding human leukocyte antigen molecules and genes encoding components of the interferon lambda innate immune system drive viral polymorphism. Additionally, we show that IFNL4 genotypes determine HCV viral load through a mechanism dependent on a specific amino acid residue in the HCV NS5A protein. These findings highlight the interplay between the innate immune system and the viral genome in HCV control.

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Titre: Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus
Créateurs - sans rôle: M. Azim Ansari - Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
Vincent Pedergnana - Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
Camilla L. C. Ip - Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
Andrea Magri - University of Oxford
Annette Von Delft - Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res, Oxford, England
David Bonsall - University of Oxford
Nimisha Chaturvedi - Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland
Istvan Bartha - Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland
David Smith - Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res, Oxford, England
George Nicholson - Univ Oxford, Dept Stat, Oxford, England
Gilean McVean - Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
Amy Trebes - University of Oxford
Paolo Piazza - University of Oxford
Jacques Fellay - Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland
Graham Cooke - Imperial Coll London, Wright Fleming Inst, London, England
Graham R. Foster - Queen Mary University of London
Emma Hudson - University of Oxford
John McLauchlan - University of Glasgow
Peter Simmonds - Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res, Oxford, England
Rory Bowden - Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
Paul Klenerman - Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res, Oxford, England
Eleanor Barnes - Univ Oxford, Nuffield Dept Med, Peter Medawar Bldg Pathogen Res, Oxford, England
Chris C. A. Spencer - Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
STOP-HCV Consortium
Détails de publication: Nature genetics, Vol.49(5), pp.666-673
Éditeur: NATURE PORTFOLIO
Nombre de pages: 10
Note de subvention: U19AI082630 / US National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 090532/Z/09/Z; 109965MA; 097364/Z/11/Z; 100956/Z/13/Z / Wellcome Trust BB/N008553/1 / BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) Medical Research Foundation; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) MC.UU.12014/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) C0365 / Medical Research Foundation; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) BRC of the Imperial College NHS Trust G0400802; G1001738; MR/P025064/1; MC_EX_UU_G1000717; G0801976; MR/K01532X/1; G1100247; MC_UU_12014/1; MC_UP_A390_1107 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 097364/Z/11/Z / Wellcome Trust
Identifiants: 99158951909311
Unité académique: Maladies Infectieuses et Vecteurs : Ecologie, Génétique, Evolution et Contrôle - MIVEGEC
Langue: English
Type de ressource: Journal article