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Interferon lambda 4 impacts the genetic diversity of hepatitis C virus.
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; Hudson, Emma; Bowden, Rory; Patel, Arvind H; Foster, Graham R; Irving, William L; Agarwal, Kosh; Thomson, Emma C; Simmonds, Peter; Klenerman, Paul; Holmes, Chris; Barnes, Eleanor; Spencer, Chris Ca; McLauchlan, John; Pedergnana, Vincent.
Affiliation
  • Ansari MA; Wellcome Centre Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Aranday-Cortes E; MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Glasgow, United Kingdom.
  • Ip CL; Wellcome Centre Human Genetics, University of Oxford, Oxford, United Kingdom.
  • da Silva Filipe A; MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Glasgow, United Kingdom.
  • Lau SH; MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Glasgow, United Kingdom.
  • Bamford C; MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Glasgow, United Kingdom.
  • Bonsall D; Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, United Kingdom.
  • Trebes A; Wellcome Centre Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Piazza P; Wellcome Centre Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Sreenu V; MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Glasgow, United Kingdom.
  • Cowton VM; MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Glasgow, United Kingdom.
  • Hudson E; Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, United Kingdom.
  • Bowden R; Wellcome Centre Human Genetics, University of Oxford, Oxford, United Kingdom.
  • Patel AH; MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Glasgow, United Kingdom.
  • Foster GR; Blizard Institute, Queen Mary University, London, United Kingdom.
  • Irving WL; National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom.
  • Agarwal K; Institute of Liver Studies, King's College Hospital, London, United Kingdom.
  • Thomson EC; MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Glasgow, United Kingdom.
  • Simmonds P; Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, United Kingdom.
  • Klenerman P; Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, United Kingdom.
  • Holmes C; Department of Statistics, University of Oxford, Oxford, United Kingdom.
  • Barnes E; Nuffield Department of Medicine and the Oxford NIHR BRC, University of Oxford, Oxford, United Kingdom.
  • Spencer CC; Wellcome Centre Human Genetics, University of Oxford, Oxford, United Kingdom.
  • McLauchlan J; MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, Glasgow, United Kingdom.
  • Pedergnana V; Wellcome Centre Human Genetics, University of Oxford, Oxford, United Kingdom.
Elife ; 82019 09 03.
Article in En | MEDLINE | ID: mdl-31478835
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Antiviral Agents / Genetic Variation / Interleukins / Hepatitis C / Hepacivirus / Immunologic Factors Limits: Humans Language: En Journal: Elife Year: 2019 Document type: Article Affiliation country: Reino Unido Country of publication: Reino Unido

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Antiviral Agents / Genetic Variation / Interleukins / Hepatitis C / Hepacivirus / Immunologic Factors Limits: Humans Language: En Journal: Elife Year: 2019 Document type: Article Affiliation country: Reino Unido Country of publication: Reino Unido