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Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes

Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes The study of hepatitis C virus (HCV), a major cause of chronic liver disease, has been hampered by the lack of a cell culture system supporting its replication. Here, we have successfully generated infectious pseudo-particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene packaged within these HCV pseudo-particles allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes as well as hepato-carcinoma 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 by some anti-E2 monoclonal antibodies. In addition, these pseudo-particles allowed investigation of the role of putative HCV receptors. Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. Altogether, these studies indicate that these pseudo-particles may mimic the early infection steps of parental HCV and will be suitable for the development of much needed new antiviral therapies. hepatitis viral assembly glycoproteins receptor neutralization Footnotes ↵ * Abbreviations used in this paper: GFP, green fluorescent protein; HCV, hepatitis C virus; HCVpp, HCV pseudo-particles; LDLr, low density lipoprotein receptor; MLV, murine leukemia virus; PBMC, peripheral blood mononuclear cell; TU, transducing unit; VLDL, very low density lipoprotein. Submitted: 3 October 2002 Accepted: 15 January 2003 Revision received 3 January 2003 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes

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References (98)

Publisher
Rockefeller University Press
Copyright
© 2003 Rockefeller University Press
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.20021756
Publisher site
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Abstract

The study of hepatitis C virus (HCV), a major cause of chronic liver disease, has been hampered by the lack of a cell culture system supporting its replication. Here, we have successfully generated infectious pseudo-particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene packaged within these HCV pseudo-particles allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes as well as hepato-carcinoma 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 by some anti-E2 monoclonal antibodies. In addition, these pseudo-particles allowed investigation of the role of putative HCV receptors. Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. Altogether, these studies indicate that these pseudo-particles may mimic the early infection steps of parental HCV and will be suitable for the development of much needed new antiviral therapies. hepatitis viral assembly glycoproteins receptor neutralization Footnotes ↵ * Abbreviations used in this paper: GFP, green fluorescent protein; HCV, hepatitis C virus; HCVpp, HCV pseudo-particles; LDLr, low density lipoprotein receptor; MLV, murine leukemia virus; PBMC, peripheral blood mononuclear cell; TU, transducing unit; VLDL, very low density lipoprotein. Submitted: 3 October 2002 Accepted: 15 January 2003 Revision received 3 January 2003

Journal

The Journal of Experimental Medicine – Rockefeller University Press

Published: Mar 3, 2003

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