Viral and Cellular Determinants of Hepatitis C Virus Envelope-Heparan Sulfate Interaction
No Thumbnail Available
Authors
Barth, Heidi
Schnober, Eva K.
Zhang, Fuming
Linhardt, Robert J.
Depla, Erik
Boson, Bertrand
Cosset, Francois Loic
Patel, Arvind H.
Blum, Hubert E.
Baumert, Thomas F.
Issue Date
2006-11-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Cellular binding and entry of hepatitis C virus (HCV) are the first steps of viral infection and represent a major target for antiviral antibodies and novel therapeutic strategies. We have recently demonstrated that heparan sulfate (HS) plays a key role in the binding of HCV envelope glycoprotein E2 to target cells (Barth et al., J. Biol. Chem. 278:41003-41012, 2003). In this study, we characterized the HCV-HS interaction and analyzed its inhibition by antiviral host immune responses. Using recombinant envelope glycoproteins, virus-like particles, and HCV pseudoparticles as model systems for the early steps of viral infection, we mapped viral and cellular determinants of HCV-HS interaction. HCV-HS binding required a specific HS structure that included N-sulfo groups and a minimum of 10 to 14 saccharide subunits. HCV envelope binding to HS was mediated by four viral epitopes overlapping the E2 hypervariable region 1 and E2-CD81 binding domains. In functional studies using HCV pseudoparticles, we demonstrate that HCV binding and entry are specifically inhibited by highly sulfated HS. Finally, HCV-HS binding was markedly inhibited by antiviral antibodies derived from HCV-infected individuals. In conclusion, our results demonstrate that binding of the viral envelope to a specific HS configuration represents an important step for the initiation of viral infection and is a target of antiviral host immune responses in vivo. Mapping of viral and cellular determinants of HCV-HS interaction sets the stage for the development of novel HS-based antiviral strategies targeting viral attachment and entry.
Description
Journal of Virology, 80, 10579-10590
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Viral and Cellular Determinants of Hepatitis C Virus Envelope-Heparan Sulfate Interaction, H. Barth, E. K. Schnober, F. Zhang, R. J. Linhardt, E. Depla, B. Boson, F.-L. Cosset, A. Patel, H. E. Blum, T. F. Baumert, Journal of Virology, 80, 10579-10590, 2006.
Publisher
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
0022538X