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 BowdenPaul Klenerman, Eleanor Barnes, Chris C. A. Spencer, Jonathan Ball, Diana M. Brainard, Gary Burgess, John Dillon, Charles Gore, Neil Guha, Rachel Halford, Cham Herath, Chris Holmes, Anita Howe, William Irving, Salim Khakoo, Diana Koletzki, Natasha K. Martin, Benedetta Massetto, Tamyo Mbisa, John G. McHutchison, Jane McKeating, Alec Miners, Andrea Murray, Peter J. Shaw, Paul Targett-Adams, Emma Thomson, Peter Vickerman, Nicole Zitzmann, STOP-HCV Consortium

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45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)666-673
Number of pages8
JournalNature Genetics
Volume49
Issue number5
DOIs
Publication statusPublished - 10 Apr 2017

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    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., ... STOP-HCV Consortium (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), 666-673. https://doi.org/10.1038/ng.3835