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).
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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- Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences > Tissue Infection and Repair
Clinical and Experimental Sciences > Tissue Infection and Repair - Faculties (pre 2011 reorg) > Faculty of Medicine Health & Life Sciences (pre 2011 reorg) > Medicine (pre 2011 reorg) > Cancer Sciences (pre 2011 reorg)
Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > Medicine (pre 2011 reorg) > Cancer Sciences (pre 2011 reorg) - Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > Clinical & Experimental Sciences (pre 2018 reorg) > Tissue Infection & Repair (pre 2018 reorg)
Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences > Clinical & Experimental Sciences (pre 2018 reorg) > Tissue Infection & Repair (pre 2018 reorg)
Clinical and Experimental Sciences > Clinical & Experimental Sciences (pre 2018 reorg) > Tissue Infection & Repair (pre 2018 reorg) - Current Faculties > Faculty of Environmental and Life Sciences > School of Biological Sciences
School of Biological Sciences - Faculties (pre 2018 reorg) > Faculty of Natural and Environmental Sciences (pre 2018 reorg) > Institute for Life Sciences (pre 2018 reorg)
Current Faculties > Faculty of Environmental and Life Sciences > Institute for Life Sciences > Institute for Life Sciences (pre 2018 reorg)
Institute for Life Sciences > Institute for Life Sciences (pre 2018 reorg) - Faculties (pre 2018 reorg) > Faculty of Natural and Environmental Sciences (pre 2018 reorg) > Biological Sciences (pre 2018 reorg)
Current Faculties > Faculty of Environmental and Life Sciences > School of Biological Sciences > Biological Sciences (pre 2018 reorg)
School of Biological Sciences > Biological Sciences (pre 2018 reorg) - Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences > Allergy and Inflammation Research
Clinical and Experimental Sciences > Allergy and Inflammation Research - Current Faculties > Faculty of Medicine > Cancer Sciences
Cancer Sciences - Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg)
- Current Faculties > Faculty of Medicine
- Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences
Clinical and Experimental Sciences
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