Impaired replication of hepatitis C virus containing mutations in a conserved NS5B retinoblastoma protein-binding motif.

ABSTRACT: Hepatitis C virus (HCV) downregulates the retinoblastoma tumor suppressor protein (Rb), a central cell cycle regulator which is also targeted by oncoproteins expressed by DNA tumor viruses. HCV genome replication is also enhanced in proliferating cells. Thus, it is possible that HCV interactions with host cell cycle regulators, such as Rb, have evolved to modify the intracellular environment to promote viral replication. To test this hypothesis and to determine the impact of viral regulation of Rb on HCV replication, we constructed infectious viral genomes containing mutations in the Rb-binding motif of NS5B which ablate the ability of HCV to regulate Rb. These genomes underwent replication in transfected cells but produced variably reduced virus yields. One mutant, L314A, was severely com

SUBMITTER: McGivern DR 

PROVIDER: S-EPMC2708619 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature