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Interferon lambda 4 impacts broadly on hepatitis C virus diversity

M Azim Ansari, Elihu Aranday-Cortes, Camilla LC Ip, Ana da Silva Filipe, Lau Siu Hin, Connor G G 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 CA Spencer, John McLauchlan, Vincent Pedergnana
doi: https://doi.org/10.1101/305151
M Azim Ansari
1Wellcome Centre Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
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Elihu Aranday-Cortes
2MRC-University of Glasgow, Centre for Virus Research, Sir Michael Stoker Building, 464, Bearsden Road, Glasgow, G61 1QH, UK
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Camilla LC Ip
1Wellcome Centre Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
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Ana da Silva Filipe
2MRC-University of Glasgow, Centre for Virus Research, Sir Michael Stoker Building, 464, Bearsden Road, Glasgow, G61 1QH, UK
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Lau Siu Hin
2MRC-University of Glasgow, Centre for Virus Research, Sir Michael Stoker Building, 464, Bearsden Road, Glasgow, G61 1QH, UK
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Connor G G Bamford
2MRC-University of Glasgow, Centre for Virus Research, Sir Michael Stoker Building, 464, Bearsden Road, Glasgow, G61 1QH, UK
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David Bonsall
3Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, OX1 3SY, UK
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Amy Trebes
1Wellcome Centre Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
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Paolo Piazza
1Wellcome Centre Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
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Vattipally Sreenu
2MRC-University of Glasgow, Centre for Virus Research, Sir Michael Stoker Building, 464, Bearsden Road, Glasgow, G61 1QH, UK
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Vanessa M Cowton
2MRC-University of Glasgow, Centre for Virus Research, Sir Michael Stoker Building, 464, Bearsden Road, Glasgow, G61 1QH, UK
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Emma Hudson
3Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, OX1 3SY, UK
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Rory Bowden
1Wellcome Centre Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
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Arvind H Patel
2MRC-University of Glasgow, Centre for Virus Research, Sir Michael Stoker Building, 464, Bearsden Road, Glasgow, G61 1QH, UK
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Graham R Foster
4Blizard Institute, Queen Mary University, London, E1 2AT, UK
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William L Irving
5National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, NG7 2RD, UK
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Kosh Agarwal
6Institute of Liver Studies, King’s College Hospital, London, United Kingdom
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Emma C Thomson
2MRC-University of Glasgow, Centre for Virus Research, Sir Michael Stoker Building, 464, Bearsden Road, Glasgow, G61 1QH, UK
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Peter Simmonds
3Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, OX1 3SY, UK
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Paul Klenerman
3Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, OX1 3SY, UK
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Chris Holmes
7Department of Statistics, University of Oxford,OX1 3LB
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Eleanor Barnes
3Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, OX1 3SY, UK
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Chris CA Spencer
1Wellcome Centre Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
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John McLauchlan
2MRC-University of Glasgow, Centre for Virus Research, Sir Michael Stoker Building, 464, Bearsden Road, Glasgow, G61 1QH, UK
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Vincent Pedergnana
1Wellcome Centre Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
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Abstract

Type III interferons (IFN-λ) are part of the innate immune response to hepatitis C virus (HCV) infection however the specific role of IFN-λ4 and the nature of the viral adaption to this pressure have not been defined. Here we use paired genome-wide human and viral genetic data in 485 patients infected with HCV genotype 3a to explore the role of IFN-λ4 on HCV evolution during chronic infection. We show that genetic variations within the host IFNL4 locus have a broad and systematic impact on HCV amino acid diversity. We also demonstrate that this impact is larger in patients producing a more active form of IFN-λ4 protein compared to the less active form. A similar observation was noted for viral load. We conclude that IFN-λ4 protein is a likely causal agent driving widespread HCV amino acid changes and associated with viral load and possibly other clinical and biological outcomes of HCV infection.

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Posted April 20, 2018.
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Interferon lambda 4 impacts broadly on hepatitis C virus diversity
M Azim Ansari, Elihu Aranday-Cortes, Camilla LC Ip, Ana da Silva Filipe, Lau Siu Hin, Connor G G 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 CA Spencer, John McLauchlan, Vincent Pedergnana
bioRxiv 305151; doi: https://doi.org/10.1101/305151
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Interferon lambda 4 impacts broadly on hepatitis C virus diversity
M Azim Ansari, Elihu Aranday-Cortes, Camilla LC Ip, Ana da Silva Filipe, Lau Siu Hin, Connor G G 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 CA Spencer, John McLauchlan, Vincent Pedergnana
bioRxiv 305151; doi: https://doi.org/10.1101/305151

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