Cell culture-grown hepatitis C virus is infectious <i>in vivo</i> and can be recultured <i>in vitro</i>

TLDR

Hepatitis C virus causes chronic liver disease that can progress to cirrhosis and hepatocellular carcinoma, yet current therapies are inadequate and progress is limited by inefficient culture systems. The study aims to show that the HCVcc strain FL‑J6/JFH can establish long‑term infections in chimpanzees and human‑liver‑grafted mice. This was achieved by employing a genotype 2a infectious clone that replicates and produces infectious virus in cell culture, enabling infection of the animal models. Virus recovered from these animals was highly infectious in cell culture, with lower buoyant density correlating with increased infectivity, thereby extending the HCVcc system’s utility for complete life‑cycle dissection.

Abstract

Hepatitis C virus (HCV) is a major cause of chronic liver disease, frequently progressing to cirrhosis and increased risk of hepatocellular carcinoma. Current therapies are inadequate and progress in the field has been hampered by the lack of efficient HCV culture systems. By using a recently described HCV genotype 2a infectious clone that replicates and produces infectious virus in cell culture (HCVcc), we report here that HCVcc strain FL-J6/JFH can establish long-term infections in chimpanzees and in mice containing human liver grafts. Importantly, virus recovered from these animals was highly infectious in cell culture, demonstrating efficient ex vivo culture of HCV. The improved infectivity of animal-derived HCV correlated with virions of a lower average buoyant density than HCVcc, suggesting that physical association with low-density factors influences viral infectivity. These results greatly extend the utility of the HCVcc genetic system to allow the complete in vitro and in vivo dissection of the HCV life cycle.