Functional Characterization of Core Genes from Patients with Acute Hepatitis C Virus Infection

The HCV core protein is implicated in diverse aspects of HCV-induced pathogenesis. There is a paucity of information on core in acute hepatitis C infection. We analyzed core gene sequences and protein functions from 13 patients acutely infected with HCV genotype 1. While core isolates differed slightly between patients, core quasispecies were relatively homogeneous within a patient. In 2 of 4 patients studied temporally, core quasispecies did not change over time. Comparison with more than 2700 published core isolates indicated that amino acid changes from a prototype reference strain found in acute core isolates were present in chronically infected persons at low frequency (6.4%, range 0-32%). Core isolates associated with lipid droplets (LDs) to similar degrees in Huh7 cells. Core diffusion in cells was not affected by non-conservative changes F130L and G161S in the lipid targeting domain of core. Core isolates inhibited ISRE- and NF-κB-dependent transcription, and TNF-α- induced nuclear translocation of NF-κB and were also secreted from Huh7 cells. The data suggest that upon transmission, core quasispecies undergo genetic homogenization associated with amino acid changes that are rarely found in chronic infection, and that despite genetic variation, acute core isolates retain similar functions in vitro.