Development of HCV envelope-pseudotyped virus particles for evaluation of HCV entry inhibitors and cellular proteases involved in HCV envelope processing

Hepatitis C virus (HCV) infection remains a daunting challenge to public health, although tremendous progress has been made recently in anti-HCV research. New effective treatments without side-effects are urgently needed. Viral entry represents a multifaceted target for anti-HCV intervention. To establish an assay for discovery and development of HCV entry inhibitors, infectious pseudo-particles (HCVpp) were generated by incorporating unmodified and functional HCV genotype 1 E1E2 glycoproteins into retroviral backbone of HIV-1. Well-characterized compounds (APVT-CV-N, IFN-α, Ribavirin, and Erlotinib) and antibodies (anti-E2 and anti-CD81) were utilized to validate the system. Results demonstrated that the newly established platform of HCVpp can serve as an important tool for the study of virus entry and for the discovery and development of new anti-HCV drugs. Furthermore, cellular protease inhibitors were tested in an effort to determine which proteases are involved in the processing of HCV E1E2 glycoproteins and in their subsequent incorporation into HCVpp.