Highly replicating hepatitis C virus variants emerge in immunosuppressed patients causing severe disease.

ABSTRACT: Hepatitis C virus (HCV) exists as a heterogenous quasispecies, but the phenotypic consequences of viral variability are widely unexplored. Here we identify a replication enhancing domain (ReED) in non-structural protein 5A conferring high replication fitness to clinical isolates. Accumulation of mutations in the ReED mediates high genome replication capacity. In a cohort of liver transplant patients, high replicator variants are exclusively found in individuals with severe disease outcome, suggesting that high viral replication fitness is associated with increased viral pathogenesis. Analysis of large sequence cohorts reveals that overall only 10% of viral genomes show genetic signatures of high replicators, which are enriched in recipients of liver transplantations, patients developing he

SUBMITTER: Rothhaar P 

PROVIDER: S-EPMC12686413 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature