Researchers have developed infectious hepatitis C virus (HCV) pseudo-particles containing functional E1-E2 envelope protein complexes, which can be used to study HCV infection and develop new antiviral therapies. These pseudo-particles were generated by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes and hepatocarcinoma cells were found to be the major targets of infection in vitro. High infectivity of the pseudo-particles required both E1 and E2 HCV glycoproteins, and was neutralized by sera from HCV-infected patients and some anti-E2 monoclonal antibodies. These pseudo-particles allowed investigation of the role of putative HCV receptors, although results suggest that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. The study indicates that these pseudo-particles may mimic the early infection steps of parental HCV and are suitable for the development of new antiviral therapies. The study also highlights the importance of E1 and E2 glycoproteins in HCV entry and the need for further research into HCV receptors and entry mechanisms.Researchers have developed infectious hepatitis C virus (HCV) pseudo-particles containing functional E1-E2 envelope protein complexes, which can be used to study HCV infection and develop new antiviral therapies. These pseudo-particles were generated by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes and hepatocarcinoma cells were found to be the major targets of infection in vitro. High infectivity of the pseudo-particles required both E1 and E2 HCV glycoproteins, and was neutralized by sera from HCV-infected patients and some anti-E2 monoclonal antibodies. These pseudo-particles allowed investigation of the role of putative HCV receptors, although results suggest that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. The study indicates that these pseudo-particles may mimic the early infection steps of parental HCV and are suitable for the development of new antiviral therapies. The study also highlights the importance of E1 and E2 glycoproteins in HCV entry and the need for further research into HCV receptors and entry mechanisms.