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Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

Interferon lambda 4 impacts the genetic diversity of hepatitis C virus
Interferon lambda 4 impacts the genetic diversity of hepatitis C virus
Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability is affected by the adaptive immune response but the contribution of other host factors is unclear. Here, we examined the role played by interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays a crucial role in spontaneous clearance or establishment of chronicity following acute infection. We performed viral genome-wide association studies using human and viral data from 485 patients of white ancestry infected with HCV genotype 3a. We demonstrate that combinations of host genetic variants, which determine IFN-λ4 protein production and activity, influence amino acid variation across the viral polyprotein - not restricted to specific viral proteins or HLA restricted epitopes - and modulate viral load. We also observed an association with viral di-nucleotide proportions. These results support a direct role for IFN-λ4 in exerting selective pressure across the viral genome, possibly by a novel mechanism.
2050-084X
1-23
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Barnes, Eleanor
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Mclauchlan, John
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Pedergnana, Vincent
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Ansari, M. Azim, Aranday-cortes, Elihu, Ip, Camilla Lc, Da Silva Filipe, Ana, Lau, Siu Hin, Bamford, Connor, Bonsall, David, Trebes, Amy, Piazza, Paolo, Sreenu, Vattipally, Cowton, Vanessa M, Ball, J., Barnes, E., Burgess, G., Cooke, G, Dillon, J, Foster, G., Gore, C., Guha, N, Halford, R, Holmes, C., Hudson, Emma, Hutchinson, S, Irving, W., Khakoo, S, Klenerman, Paul, Martin, N., Mbisa, T, Mckeating, J, Mclauchlan, John, Miners, A., Murray, A, Shaw, P, Simmonds, P, Smith, S, Spencer, C, Thomson, E, Troke, P, Vickerman, P, Zitzmann, N, Hudson, Emma, Bowden, Rory, Patel, Arvind H, Foster, Graham R, Irving, William L, Agarwal, Kosh, Thomson, Emma C, Simmonds, P., Klenerman, Paul, Holmes, Chris, Barnes, Eleanor, Spencer, Chris Ca, Mclauchlan, John and Pedergnana, Vincent (2019) Interferon lambda 4 impacts the genetic diversity of hepatitis C virus. eLife, 8, 1-23, [e42463]. (doi:10.7554/eLife.42463).

Record type: Article

Abstract

Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability is affected by the adaptive immune response but the contribution of other host factors is unclear. Here, we examined the role played by interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays a crucial role in spontaneous clearance or establishment of chronicity following acute infection. We performed viral genome-wide association studies using human and viral data from 485 patients of white ancestry infected with HCV genotype 3a. We demonstrate that combinations of host genetic variants, which determine IFN-λ4 protein production and activity, influence amino acid variation across the viral polyprotein - not restricted to specific viral proteins or HLA restricted epitopes - and modulate viral load. We also observed an association with viral di-nucleotide proportions. These results support a direct role for IFN-λ4 in exerting selective pressure across the viral genome, possibly by a novel mechanism.

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Accepted/In Press date: 8 August 2019
Published date: 3 September 2019

Identifiers

Local EPrints ID: 435721
URI: http://eprints.soton.ac.uk/id/eprint/435721
ISSN: 2050-084X
PURE UUID: ab0f1e50-9ff1-41d2-ac70-ee2dedca729f

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Date deposited: 19 Nov 2019 17:30
Last modified: 16 Dec 2019 17:30

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Contributors

Author: M. Azim Ansari
Author: Elihu Aranday-cortes
Author: Camilla Lc Ip
Author: Ana Da Silva Filipe
Author: Siu Hin Lau
Author: Connor Bamford
Author: David Bonsall
Author: Amy Trebes
Author: Paolo Piazza
Author: Vattipally Sreenu
Author: Vanessa M Cowton
Author: J. Ball
Author: E. Barnes
Author: G. Burgess
Author: G Cooke
Author: J Dillon
Author: G. Foster
Author: C. Gore
Author: N Guha
Author: R Halford
Author: C. Holmes
Author: Emma Hudson
Author: S Hutchinson
Author: W. Irving
Author: S Khakoo
Author: Paul Klenerman
Author: N. Martin
Author: T Mbisa
Author: J Mckeating
Author: John Mclauchlan
Author: A. Miners
Author: A Murray
Author: P Shaw
Author: P Simmonds
Author: S Smith
Author: C Spencer
Author: E Thomson
Author: P Troke
Author: P Vickerman
Author: N Zitzmann
Author: Emma Hudson
Author: Rory Bowden
Author: Arvind H Patel
Author: Graham R Foster
Author: William L Irving
Author: Kosh Agarwal
Author: Emma C Thomson
Author: P. Simmonds
Author: Paul Klenerman
Author: Chris Holmes
Author: Eleanor Barnes
Author: Chris Ca Spencer
Author: John Mclauchlan
Author: Vincent Pedergnana

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