Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

M. Azim Ansari; Elihu Aranday-Cortes; Camilla L. C. Ip; Ana da Silva Filipe; Siu Hin Lau; Connor Bamford; David Bonsall; Amy Trebes; Paolo Piazza; Vattipally Sreenu; Vanessa M. Cowton; STOP-HCV Consortium; Emma Hudson; Rory Bowden; Arvind H. Patel; Graham R. Foster; William L. Irving; Kosh Agarwal; Emma C. Thomson; Peter Simmonds; Paul Klenerman; Chris Holmes; Eleanor Barnes; Chris C. A. Spencer; John McLauchlan; Vincent Pedergnana

doi:10.7554/eLife.42463

Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

M. Azim Ansari, Elihu Aranday-Cortes, Camilla L. C. Ip, Ana da Silva Filipe, Siu Hin Lau, Connor Bamford, David Bonsall, Amy Trebes, Paolo Piazza, Vattipally Sreenu, Vanessa M. Cowton, STOP-HCV Consortium, Emma Hudson, Rory Bowden, Arvind H. Patel, Graham R. Foster, William L. Irving, Kosh Agarwal, Emma C. Thomson, Peter SimmondsPaul Klenerman, Chris Holmes, Eleanor Barnes, Chris C. A. Spencer, John McLauchlan, Vincent Pedergnana (Lead / Corresponding author)

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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.

Original language	English
Article number	e42463
Pages (from-to)	1-23
Number of pages	23
Journal	eLife
Volume	8
DOIs	https://doi.org/10.7554/eLife.42463
Publication status	Published - 3 Sept 2019

ASJC Scopus subject areas

General Neuroscience
General Immunology and Microbiology
General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7554/eLife.42463Licence: CC BY

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Ansari, M. A., Aranday-Cortes, E., Ip, C. L. C., da Silva Filipe, A., Lau, S. H., Bamford, C., Bonsall, D., Trebes, A., Piazza, P., Sreenu, V., Cowton, V. M., STOP-HCV Consortium, Hudson, E., Bowden, R., Patel, A. H., Foster, G. R., Irving, W. L., Agarwal, K., Thomson, E. C., ... Pedergnana, V. (2019). Interferon lambda 4 impacts the genetic diversity of hepatitis C virus. eLife, 8, 1-23. Article e42463. https://doi.org/10.7554/eLife.42463

@article{3696f930000248c1aaa70b76c3ecdf8e,

title = "Interferon lambda 4 impacts the genetic diversity of hepatitis C virus",

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.",

author = "Ansari, {M. Azim} and Elihu Aranday-Cortes and Ip, {Camilla L. C.} and {da Silva Filipe}, Ana and Lau, {Siu Hin} and Connor Bamford and David Bonsall and Amy Trebes and Paolo Piazza and Vattipally Sreenu and Cowton, {Vanessa M.} and {STOP-HCV Consortium} and Emma Hudson and Rory Bowden and Patel, {Arvind H.} and Foster, {Graham R.} and Irving, {William L.} and Kosh Agarwal and Thomson, {Emma C.} and Peter Simmonds and Paul Klenerman and Chris Holmes and Eleanor Barnes and Spencer, {Chris C. A.} and John McLauchlan and Vincent Pedergnana and J. Ball and G. Burgess and G. Cooke and J. Dillon and C. Gore and N. Guha and R. Halford and S. Hutchinson and S. Khakoo and N. Martin and T. Mbisa and J. McKeating and A. Miners and A. Murray and P. Shaw and S. Smith and P. Troke and P. Vickerman and N. Zitzmann",

note = "{\textcopyright} 2019, Ansari et al.",

year = "2019",

month = sep,

day = "3",

doi = "10.7554/eLife.42463",

language = "English",

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journal = "eLife",

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Ansari, MA, Aranday-Cortes, E, Ip, CLC, da Silva Filipe, A, Lau, SH, Bamford, C, Bonsall, D, Trebes, A, Piazza, P, Sreenu, V, Cowton, VM, STOP-HCV Consortium, Hudson, E, Bowden, R, Patel, AH, Foster, GR, Irving, WL, Agarwal, K, Thomson, EC, Simmonds, P, Klenerman, P, Holmes, C, Barnes, E, Spencer, CCA, McLauchlan, J & Pedergnana, V 2019, 'Interferon lambda 4 impacts the genetic diversity of hepatitis C virus', eLife, vol. 8, e42463, pp. 1-23. https://doi.org/10.7554/eLife.42463

TY - JOUR

T1 - Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

AU - Ansari, M. Azim

AU - Aranday-Cortes, Elihu

AU - Ip, Camilla L. C.

AU - da Silva Filipe, Ana

AU - Lau, Siu Hin

AU - Bamford, Connor

AU - Bonsall, David

AU - Trebes, Amy

AU - Piazza, Paolo

AU - Sreenu, Vattipally

AU - Cowton, Vanessa M.

AU - STOP-HCV Consortium

AU - Hudson, Emma

AU - Bowden, Rory

AU - Patel, Arvind H.

AU - Foster, Graham R.

AU - Irving, William L.

AU - Agarwal, Kosh

AU - Thomson, Emma C.

AU - Simmonds, Peter

AU - Klenerman, Paul

AU - Holmes, Chris

AU - Barnes, Eleanor

AU - Spencer, Chris C. A.

AU - McLauchlan, John

AU - Pedergnana, Vincent

AU - Ball, J.

AU - Burgess, G.

AU - Cooke, G.

AU - Dillon, J.

AU - Gore, C.

AU - Guha, N.

AU - Halford, R.

AU - Hutchinson, S.

AU - Khakoo, S.

AU - Martin, N.

AU - Mbisa, T.

AU - McKeating, J.

AU - Miners, A.

AU - Murray, A.

AU - Shaw, P.

AU - Smith, S.

AU - Troke, P.

AU - Vickerman, P.

AU - Zitzmann, N.

PY - 2019/9/3

Y1 - 2019/9/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85071768533&partnerID=8YFLogxK

U2 - 10.7554/eLife.42463

DO - 10.7554/eLife.42463

M3 - Article

C2 - 31478835

SN - 2050-084X

VL - 8

SP - 1

EP - 23

JO - eLife

JF - eLife

M1 - e42463

ER -

Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

Abstract

ASJC Scopus subject areas

UN SDGs

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