Hepatitis C virus (HCV), the sole member of the Hepacivirus genus of the Flaviviridae family, is an enveloped virus with a positive-sense single-stranded RNA genome of 9600 nucleotides. HCV virions mainly infect hepatocytes, entering via specific receptors and clathrin-mediated endocytosis to release their genome from acidified endosomes.1 Over 170 million people worldwide are infected with HCV, and 80–85% of these develop chronic hepatitis C, which in a sizeable portion (up to 20%) leads to cirrhosis, hepatic failure or hepatocellular carcinoma. Current HCV treatment is based on the antiviral action of interferon α (IFNα) in combination with ribavirin, although this clears the virus in only 40–55% of patients.

IFNα plays a central role in the innate immune system by inducing an antiviral state in target cells,2 most notably for HCV by inhibiting viral replication.3 However, it is less clear whether IFNα initiates specific actions to limit HCV infections, such as restricting virion attachment and/or entry into hepatocytes. In this edition of Gut (see page 10.1136/gut.2006.111443), Murao et al4 demonstrate in vitro that IFNα decreases cell surface expression of scavenger receptor class B type I (SR-BI), a pivotal molecule in early stages of the HCV life cycle. Before discussing their findings, however, we first describe the molecular ensemble of host cellular factors which orchestrate HCV entry.

Until the last decade, HCV research was hampered by lack of infectious clones and an inability to propagate the virus in cultured liver cells. Introduction of the HCV replicon system (a self-replicating subgenomic construct)5 allowed studies of viral replication, …