Chaturvedi, NimishaSvarovskaia, Evguenia S.Mo, HongmeiOsinusi, Anu O.Brainard, Diana M.Subramanian, G. ManiMcHutchison, John G.Zeuzem, StefanFellay, Jacques2019-09-192019-09-192019-09-192019-09-0310.7554/eLife.42542https://infoscience.epfl.ch/handle/20.500.14299/161273WOS:000484180700001Genetic polymorphism in the interferon lambda (IFN-lambda) region is associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to interferon-based treatment. Here, we evaluate associations between IFN-l polymorphism and HCV variation in 8729 patients (Europeans 77%, Asians 13%, Africans 8%) infected with various viral genotypes, predominantly 1a (41%), 1b (22%) and 3a (21%). We searched for associations between rs12979860 genotype and variants in the NS3, NS4A, NS5A and NS5B HCV proteins. We report multiple associations in all tested proteins, including in the interferon-sensitivity determining region of NS5A. We also assessed the combined impact of human and HCV variation on pretreatment viral load and report amino acids associated with both IFN-l polymorphism and HCV load across multiple viral genotypes. By demonstrating that IFN-l variation leaves a large footprint on the viral proteome, we provide evidence of pervasive viral adaptation to innate immune pressure during chronic HCV infection.BiologyLife Sciences & Biomedicine - Other Topicsgenetic-variationglobal epidemiologyil28bsubstitutionsclearanceevolutionsubtypestherapytext::journal::journal article::research article