Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

Ansari, M Azim; Aranday-Cortes, Elihu; Lc, Camilla; Da Silva Filipe, Ana; Hin, Lau Siu; Bamford, Connor G.G.; 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 C.A.; McLauchlan, John; Pedergnana, Vincent

Abstract

© Ansari et al. 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-l4) on HCV diversity; IFN-l4 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-l4 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-l4 in exerting selective pressure across the viral genome, possibly by a novel mechanism.

Citation

Ansari, M. A., Aranday-Cortes, E., Lc, C., Da Silva Filipe, A., Hin, L. S., Bamford, C. G., …Pedergnana, V. (2019). Interferon lambda 4 impacts the genetic diversity of hepatitis C virus. eLife, 2019(8), 1-23. https://doi.org/10.7554/eLife.42463

• Journal Article Type: Article
• Acceptance Date: Aug 8, 2019
• Online Publication Date: Sep 3, 2019
• Publication Date: Sep 3, 2019
• Deposit Date: Aug 13, 2019
• Publicly Available Date: Aug 13, 2019
• Journal: eLife
• Electronic ISSN: 2050-084X
• Publisher: eLife Sciences Publications
• Peer Reviewed: Peer Reviewed
• Volume: 2019
• Issue: 8
• Article Number: e42463
• Pages: 1-23
• DOI: https://doi.org/10.7554/eLife.42463
• Keywords: General Biochemistry, Genetics and Molecular Biology; General Immunology and Microbiology; General Neuroscience; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/2422282
• Publisher URL: https://elifesciences.org/articles/42463