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Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus

Lavillette, Dimitri; Tarr, Alexander W.; Voisset, Cécile; Donot, Peggy; Bartosch, Birke; Bain, Christine; Patel, Arvind H.; Dubuisson, Jean; Ball, Jonathan K.; Cosset, François Loïc

Authors

Dimitri Lavillette

Cécile Voisset

Peggy Donot

Birke Bartosch

Christine Bain

Arvind H. Patel

Jean Dubuisson

Jonathan K. Ball

François Loïc Cosset



Abstract

Because of the lack of a robust cell culture system, relatively little is known about the molecular details of the cell entry mechanism for hepatitis C virus (HCV). Recently, we described infectious HCV pseudo-particles (HCVpp) that were generated by incorporating unmodified HCV E1E2 glycoproteins into the membrane of retroviral core particles. These initial studies, performed with E1E2 glycoproteins of genotype 1, noted that HCVpp closely mimic the cell entry and neutralization properties of parental HCV. Because sequence variations in E1 and E2 may account for differences in tropism, replication properties, neutralization, and response to treatment in patients infected with different genotypes, we investigated the functional properties of HCV envelope glycoproteins from different genotypes/subtypes. Our studies indicate that hepatocytes were preferential targets of infection in vitro, although HCV replication in extrahepatic sites has been reported in vivo. Receptor competition assays using antibodies against the CD81 ectodomain as wel as ectopic expression of CD81 in CD81-deficient HepG2 cells indicated that CD81 is used by all the different genotypes/subtypes analyzed to enter the cells. However, by silencing RNA (siRNA) interference assays, our results show that the level of Scavenger Receptor Class-B Type-I (SR-BI) needed for efficient infection varies between genotypes and subtypes. Finally, sera from chronic HCV carriers were found to exhibit broadly reactive activities that inhibited HCVpp cell entry, but failed to neutralize all the different genotypes. In conclusion, we characterize common steps in the cell entry pathways of the major HCV genotypes that should provide clues for the development of cell entry inhibitors and vaccines.

Citation

Lavillette, D., Tarr, A. W., Voisset, C., Donot, P., Bartosch, B., Bain, C., Patel, A. H., Dubuisson, J., Ball, J. K., & Cosset, F. L. (2005). Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus. Hepatology, 41(2), 265-274. https://doi.org/10.1002/hep.20542

Journal Article Type Article
Acceptance Date Nov 5, 2004
Online Publication Date Jan 19, 2005
Publication Date 2005-02
Deposit Date Nov 9, 2022
Journal Hepatology
Print ISSN 0270-9139
Electronic ISSN 1527-3350
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 41
Issue 2
Pages 265-274
DOI https://doi.org/10.1002/hep.20542
Public URL https://nottingham-repository.worktribe.com/output/3129692
Publisher URL https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.20542