Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes.
Details
Serval ID
serval:BIB_B2FCC082A445
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes.
Journal
eLife
ISSN
2050-084X (Electronic)
ISSN-L
2050-084X
Publication state
Published
Issued date
03/09/2019
Peer-reviewed
Oui
Volume
8
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
Genetic polymorphism in the interferon lambda (IFN-λ) region is associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to interferon-based treatment. Here, we evaluate associations between IFN-λ 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-λ polymorphism and HCV load across multiple viral genotypes. By demonstrating that IFN-λ variation leaves a large footprint on the viral proteome, we provide evidence of pervasive viral adaptation to innate immune pressure during chronic HCV infection.
Keywords
Adaptation, Biological, Africa, Asia, Europe, Genotype, Hepacivirus/genetics, Hepatitis C/immunology, Hepatitis C/virology, Humans, Immunologic Factors/genetics, Interferons/genetics, Viral Load, Viral Nonstructural Proteins/genetics, Hepatitis C, genetics, genome to genome analysis, genomics, human, infectious disease, integration analysis, interferon lambda polymorphism, microbiology
Pubmed
Web of science
Open Access
Yes
Create date
13/09/2019 17:33
Last modification date
14/01/2021 10:38