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

Ansari, M. A. et al. (2017) Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus. Nature Genetics, 49(5), pp. 666-673. (doi:10.1038/ng.3835) (PMID:28394351)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McLauchlan, Professor John and Magri, Mr Andrea
Authors: Ansari, M. A., Pedergnana, V., Ip, C. L.C., Magri, A., Von Delft, A., Bonsall, D., Chaturvedi, N., Bartha, I., Smith, D., Nicholson, G., McVean, G., Trebes, A., Piazza, P., Fellay, J., Cooke, G., Foster, G. R., Hudson, E., McLauchlan, J., Simmonds, P., Bowden, R., Klenerman, P., Barnes, E., and Spencer, C. C.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Genetics
Publisher:Nature Publishing Group
ISSN:1061-4036
ISSN (Online):1546-1718
Published Online:10 April 2017
Copyright Holders:Copyright © 2017 Nature Publishing Group
First Published:First published in Nature Genetics 49(5):666-673
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656341Virus-host interactions in hepatitis C virus infectionJohn McLauchlanMedical Research Council (MRC)MC_UU_12014/1MVLS III - CENTRE FOR VIRUS RESEARCH