HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV in humanised mice.

ABSTRACT:

Objective

HCV is a major cause of chronic liver disease worldwide, but the role of neutralising antibodies (nAbs) in its natural history remains poorly defined. We analysed the in vivo role of hypervariable region 1 (HVR1) for HCV virion properties, including nAb susceptibility.

Design

Analysis of HCV from human liver chimeric mice infected with cell-culture-derived prototype genotype 2a recombinant J6/JFH1 or HVR1-deleted variant J6/JFH1_ΔHVR1 identified adaptive mutations, which were analysed by reverse genetics in Huh7.5 and CD81-deficient S29 cells. The increased in vivo genomic stability of the adapted viruses facilitated ex vivo density analysis by ultracentrifugation and in vivo neutralisation experiments addressing the role of HVR1.

Results

In vivo,

SUBMITTER: Prentoe J 

PROVIDER: S-EPMC5136728 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature