eLife · 2019
Interferon lambda 4 impacts the genetic diversity of hepatitis C virus.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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, STOP-HCV Consortium, 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
Аннотация
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.