biostudies-literatureWang ZMedical Research CouncilWellcome Trust116418https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618651biostudies-literatureUnknown44(10)Hepatitis C virus (HCV) exhibits significant genetic diversity and is a cause of severe liver complications. The viral envelope glycoproteins E1 and E2, key targets for neutralizing antibodies, are highly variable. To understand how host and viral genetic factors modulate antibody responses, we analyze genetic and antibody binding and neutralization data from 54 patients infected with HCV genotype 3a. We find that host polymorphisms in IFNL4 gene (IFNλ4-P70 generating haplotype) are associated with reduced antibody binding. Within the virus, variations at three specific E1/E2 amino acid positions and three N-glycosylation sites (including one site common to both analyses) significantly correlate with antibody binding and/or neutralization sensitivity. Furthermore, greater intra-patient divCell reportsInterplay of host and viral genetic variations in modulating antibody responses to genotype 3a hepatitis C virus: Implications for vaccine design.PMC7618651225198MR/K01532X/1220171225198/Z/22/ZMR/S007555/1MR/V031635/1200838222426/Z/21/Z200838/Z/16/Z222426220171/Z/20/ZDhir JTarr AWQuistrebert JBall JKAnsari MAMcKeating JAHumphreys IRadford PChai HNisioi AIrving WLSTOP-HCV consortiumStass RBowden TAKlenerman PWang ZBarnes EfalseInterplay of host and viral genetic variations in modulating antibody responses to genotype 3a hepatitis C virus: Implications for vaccine design.Hepatitis C virus (HCV) exhibits significant genetic diversity and is a cause of severe liver complications. The viral envelope glycoproteins E1 and E2, key targets for neutralizing antibodies, are highly variable. To understand how host and viral genetic factors modulate antibody responses, we analyze genetic and antibody binding and neutralization data from 54 patients infected with HCV genotype 3a. We find that host polymorphisms in IFNL4 gene (IFNλ4-P70 generating haplotype) are associated with reduced antibody binding. Within the virus, variations at three specific E1/E2 amino acid positions and three N-glycosylation sites (including one site common to both analyses) significantly correlate with antibody binding and/or neutralization sensitivity. Furthermore, greater intra-patient div2025-01-01T00:00:00Z2025 Oct2026-06-21T03:22:16.529Z2026-06-21T03:12:39.866ZS-EPMC76186514107662810.1016/j.celrep.2025.116418