The interaction of natural hepatitis C virus with human scavenger receptor SR‐BI/Cla1 is mediated by ApoB‐containing lipoproteins

Abstract

The possible role of candidate receptors in the cellular penetration of HCV from serum of infected patients remains unclear. SR-BI/Cla1 interacts with plasma HDL, native and modified LDL, and VLDL, and facilitates cellular cholesterol efflux to lipoprotein acceptors. SR-BI/Cla1 binds HCV E2 protein and interacts with HCV pseudotypes via the HVR1 of the E2 envelope glycoprotein. Our data reveal that functional SR-BI/Cla1 expressed on the surface of CHO cells mediates the binding and uptake of HCV from the sera of infected patients. Interaction between HCV and SR-BI/Cla1 is not sensitive to either anti-E2 or anti-HVR1 antibodies but is effectively inhibited by anti-betalipoprotein antibodies and competed out by apoB-containing lipoproteins and notably by VLDL. We interpret our data to indicate that VLDL associated with or incorporated into HCV plays a critical role in the primary interaction of HCV with SR-BI/Cla1, whereas the HCV E2 protein does not. In addition, our findings in hepatoma cell lines suggest that the interaction of HCV with human hepatocytes is equally mediated, at least in a part, by VLDL, and as such may represent an alternative pathway for infection. The association of HCV with ApoB-containing lipoproteins may promote cellular uptake of this virus in the presence of neutralizing antibodies.

Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles Produced in a Humanized Liver Mouse Model

“…Thus, increasing the SR-BI expression level would improve binding of low density HCVfrg populations. This assumption is congruent with a previous demonstration that the interaction between serum-derived HCV and SR-BI was competed out by VLDL (59). Alternatively, SR-BI overexpression may prevent, at least partially, binding of viral particles to LDL receptor, which has been demonstrated to be a receptor conducive to a "non-productive" infection (60).…”

Characterization of Hepatitis C Virus Particle Subpopulations Reveals Multiple Usage of the Scavenger Receptor BI for Entry Steps

“…Overall, our data are in agreement with a previous study indicating that the cellular uptake of HCV particles derived from the plasma of HCV-infected patients can be mediated by SR-BI through its interaction with lipoprotein components harbored by the virus (28). Although there may be differences between HCVcc and patient-derived particles, e.g.…”

“…Altogether, these results indicated that HCV E2 is not at play for HCVcc attachment to SR-BI, which thus involves alternative virus surface component(s). Previous studies have underscored the association of HCV particles with ␤-lipoprotein components such as apoB, apoC-I, or apoE (17,22,28), which may contribute to HCV/SR-BI interaction. Importantly, no attachment of HCVcc particles occurred to cells expressing the M158R-mutated mouse SR-BI (Fig.…”

“…Extensive studies ex vivo using HCV derived from infected patients (27)(28)(29) and in vitro using HCV models (12, 13, 30 -34) suggest that viral entry into hepatocytes, the predominant target cells, is a complex process involving the viral E1 and E2 envelope glycoproteins and several host cell surface factors. Attachment of viral particles to the host cell are mediated by glycosaminoglycans (35,36) and/or the LDL receptor (17,27,29,37), although it is unclear whether such interactions subsequently lead to a productive infection.…”

Biochemical and Morphological Properties of Hepatitis C Virus Particles and Determination of Their Lipidome

“…Likewise, apoB-containing lipoproteins (27) or high density lipoprotein (HDL) (28) appear to facilitate the interaction of HCV pseudoparticles or cell culture-grown HCV with scavenger receptor class B type I (SR-BI) (29). The exchangeable apolipoprotein apoCI, which is predominantly present in HDL, seems to interact with HCV particles via hypervariable region 1 (HVR1) in the N terminus of E2 thus promoting interaction and fusion of the HCV envelope with cellular membranes (30,31).…”