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Nat Genet. 2017 May;49(5):666-673. doi: 10.1038/ng.3835. Epub 2017 Apr 10.

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

Author information

1
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
2
Oxford Martin School, University of Oxford, Oxford, UK.
3
Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine and the NIHR Oxford BRC, University of Oxford, Oxford, UK.
4
School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
5
Department of Statistics, University of Oxford, Oxford, UK.
6
Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
7
Wright-Fleming Institute, Imperial College London, London, UK.
8
Queen Mary University of London, London, UK.
9
MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.

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.

PMID:
28394351
PMCID:
PMC5873514
DOI:
10.1038/ng.3835
[Indexed for MEDLINE]
Free PMC Article

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