1. Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus.
- Author
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Ansari MA, Pedergnana V, L C Ip 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 GR, Hudson E, McLauchlan J, Simmonds P, Bowden R, Klenerman P, Barnes E, and Spencer CCA
- Subjects
- Alleles, Genetic Variation, Genotype, HLA Antigens genetics, Hepacivirus physiology, Hepatitis C, Chronic virology, Host-Pathogen Interactions genetics, Humans, Interleukins genetics, Logistic Models, Principal Component Analysis, Viral Load genetics, Viral Nonstructural Proteins genetics, Adaptive Immunity genetics, Genome, Human genetics, Genome, Viral genetics, Hepacivirus genetics, Hepatitis C, Chronic genetics, Immunity, Innate genetics
- 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.
- Published
- 2017
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