Initiation of hepatitis C virus infection is dependent on cholesterol and cooperativity between CD81 and scavenger receptor B type I.
In the past several years, a number of cellular proteins have been identified as candidate entry receptors for hepatitis C virus (HCV) by using surrogate models of HCV infection. Among these, the tetraspanin CD81 and scavenger receptor B type I (SR-BI), both of which localize to specialized plasma membrane domains enriched in cholesterol, have been suggested to be key players in HCV entry. In the current study, we used a recently developed in vitro HCV infection system to demonstrate that both CD81 and SR-BI are required for authentic HCV infection in vitro, that they function cooperatively to initiate HCV infection, and that CD81-mediated HCV entry is, in part, dependent on membrane cholesterol.
Kapadia
Sharookh B
SB
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Barth
Heidi
H
Baumert
Thomas
T
McKeating
Jane A
JA
Chisari
Francis V
FV
D000924:Anticholesteremic Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D002784:Cholesterol / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects / Q000472:pathogenicity*; D006801:Humans; D012367:RNA, Viral / Q000378:metabolism; D012093:Replicon / Q000187:drug effects; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D060225:Tetraspanin 28; D047392:beta-Cyclodextrins / Q000494:pharmacology
D000924:Anticholesteremic Agents; D015703:Antigens, CD; C554798:CD81 protein, human; D012367:RNA, Viral; D051122:Scavenger Receptors, Class B; D060225:Tetraspanin 28; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol