Cell Entry of Hepatitis C Virus Requires a Set of Co-receptors That Include the CD81 Tetraspanin and the SR-B1 Scavenger Receptor*

By B. Bartosch, A. Vitelli, Christelle Granier, C. Goujon, J. Dubuisson, S. Pascale, E. Scarselli, R. Cortese, A. Nicosia, F. Cosset. Journal of Biological Chemistry, 2003

687 citations recorded by the source corpus.

Several cell surface molecules have been proposed as receptor candidates, mediating cell entry of hepatitis C virus (HCV) on the basis of their physical association with virions or with soluble HCV E2 glycoproteins. However, due to the lack of infectious HCV particles, evidence that these receptor candidates support infection was missing. Using our recently described infectious HCV pseudotype particles (HCVpp) that display functional E1E2 glycoprotein complexes, here we show that HCV is a pH-dependent virus, implying that its receptor component(s) mediate virion internalization by endocytosis. Expression of the CD81 tetraspanin in non-permissive CD81-negative hepato-carcinoma cells was sufficient to restore susceptibility to HCVpp infection, confirming its critical role as a cell attachment factor. As a cell surface molecule likely to mediate endosomal trafficking, we demonstrate that the human scavenger receptor class B type 1 (SR-B1), a high-density lipoprotein-internalization molecule that we previously proposed as a novel HCV receptor candidate due to its affinity with E2 glycoproteins, is required for infection of CD81-expressing hepatic cells. By receptor competition assays, we found that SR-B1 antibodies that blocked binding of soluble E2 could prevent HCVpp infectivity. Furthermore, we establish that the hyper-variable region 1 of the HCV E2 glycoprotein is a critical determinant mediating entry in SR-B1-positive cells. Finally, by correlating expression of HCV receptors and infectivity, we suggest that, besides CD81 and SR-B1, additional hepatocyte-specific co-factor(s) are necessary for HCV entry.

Subfields: Hepatology, Radiology, Nuclear Medicine and Imaging, Rheumatology

View Paper: https://www.semanticscholar.org/paper/4bf82262b71d545d8ad86c13ee7bc9d712b77a29

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Hepatology

1. Brett D. Lindenbach Heinz-J
2. Charles M. Rice
3. S. Belouzard

In Radiology, Nuclear Medicine and Imaging

1. S. Belouzard
2. Charles M. Rice

Citations in the corpus

• Flaviviridae :T he Viruses and Their Replication (2007, background): “This phenotype may reflect a defect in virus binding and entry, because HVR1-deleted E2 binds poorly to SR-BI (628) and HCVpp with mutated or deleted HVR1 have lower SRBI–mediated and HDL-enhanced infectivity (37,38,96).”
• Hepatitis C Virus Entry Depends on Clathrin-Mediated Endocytosis (2006, methodology): “A similar partial inhibition of A-MLVpp infection with 100 nM bafilomycin A1 was previously reported (4).”