Receptor Complementation and Mutagenesis Reveal SR-BI as an Essential HCV Entry Factor and Functionally Imply Its Intra- and Extra-Cellular Domains

• DOI: 10.1371/journal.ppat.1000310
• Publication Date: 2009-02-19T23:05:20Z
• Authors: Marlène Dreux; Viet Loan Dao Thi; Judith Fresquet; Maryse Guérin; Zélie Julia; Géraldine Verney; David Durantel; Fabien Zoulim; Dimitri Lavillette; François-Loïc Cosset; Birke Bartosch
• Keywords: Ectodomain; Scavenger Receptor; CD81; Tetraspanin

HCV entry into cells is a multi-step and slow process. It believed that the initial capture of particles by glycosaminoglycans and/or lipoprotein receptors followed coordinated interactions with scavenger receptor class B type I (SR-BI), major high-density (HDL), CD81 tetraspanin, tight junction protein Claudin-1, ultimately leading to uptake cellular penetration via low-pH endosomes. Several reports have indicated HDL promotes through interaction SR-BI. This pathway remains largely elusive, although it was shown neither associates nor modulates binding In contrast importance SR-BI has only been addressed indirectly because lack in which functional complementation assays mutant could be performed. Here we identified for first time two cell types supported HCVpp HCVcc upon ectopic expression. Remarkably, undetectable expression rat hepatoma allowed unambiguous investigation human functions during entry. By expressing different mutants either line, our results revealed features intracellular domains influence infectivity without affecting stimulation induced HDL/SR-BI interaction. Conversely, positions ectodomain that, altering binding, inhibit Finally, characterized alternative determinants reducing cholesterol efflux functions, abolish HDL-mediated infection-enhancement. Altogether, demonstrate an essential factor. Moreover, highlight specific required physiological lipid transfer hijacked favor infection.