Journal
NATURE GENETICS
Volume 49, Issue 5, Pages 666-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3835
Keywords
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Categories
Funding
- Medical Research Foundation
- Medical Research Council (MRC) [MR/K01532X/1]
- Wellcome Trust [090532/Z/09/Z, 109965MA, 097364/Z/11/Z, 100956/Z/13/Z]
- MRC
- NIHR Oxford BRC
- Oxford Martin School
- BRC of the Imperial College NHS Trust
- US National Institutes of Health [U19AI082630]
- MRC [MC.UU.12014/1]
- Medical Research Foundation [C0365]
- National Institutes of Health Research (NIHR) [RP-2016-07-012] Funding Source: National Institutes of Health Research (NIHR)
- Wellcome Trust [097364/Z/11/Z] Funding Source: Wellcome Trust
- BBSRC [BB/N008553/1] Funding Source: UKRI
- MRC [MC_UU_12014/1, MR/K01532X/1, G0801976, MC_EX_UU_G1000717, MR/P025064/1, G1001738, G0400802, MC_UP_A390_1107, G1100247] Funding Source: UKRI
- Alan Turing Institute [TU/B/000062] Funding Source: researchfish
- Medical Research Council [MR/K01532X/1, MC_UP_A390_1107, MR/P025064/1, MC_UU_12014/1, MC_EX_UU_G1000717, G1001738] Funding Source: researchfish
- Medical Research Foundation [C0365] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0515-10005, 14/02/17, RP-2016-07-012] Funding Source: researchfish
- Wellcome Trust [109965/Z/15/Z, 100956/Z/13/Z] Funding Source: researchfish
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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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