In search of hepatitis C virus receptor(s)

Since the genomic sequence of HCV was determined, significant progress has been made towards understanding the functions of the HCV-encoded proteins, despite the lack of an efficient in-vitro replication system or convenient small-animal model. The identity of the receptor for HCV remains elusive, however. Low-density lipoprotein receptor, CD81, and GAGs may all act as receptors for HCV, either sequentially or by different viral quasispecies. Recent work using pseudotypic VSV bearing E1 or E2 chimeric molecules showed that entry of the E1 pseudotype can be inhibited by recombinant LDLr, whereas the E2 pseudotype is more sensitive to inhibition by recombinant CD81 or heparin. These results suggest that E1 and E2 may be responsible for interactions with different cellular molecules. It is also conceivable that additional, yet unidentified, cellular proteins are involved in viral binding and entry. Intriguingly, the reports of HCV-RNA associated with PBMC suggest that HCV infection may not be restricted to hepatocytes. Thus, separate reservoirs of virus may exist, and HCV may use different receptors to access these different cell types.