Hepatitis C virus core protein associates with detergent-resistant membranes distinct from classical plasma membrane rafts.
A subpopulation of hepatitis C virus (HCV) core protein in cells harboring full-length HCV replicons is biochemically associated with detergent-resistant membranes (DRMs) in a manner similar to that of markers of classical lipid rafts. Core protein does not, however, colocalize in immunofluorescence studies with classical plasma membrane raft markers, such as caveolin-1 and the B subunit of cholera toxin, suggesting that core protein is bound to cytoplasmic raft microdomains distinct from caveolin-based rafts. Furthermore, while both the structural core protein and the nonstructural protein NS5A associate with membranes, they do not colocalize in the DRMs. Finally, the ability of core protein to localize to the DRMs did not require other elements of the HCV polyprotein. These results may have broad implications for the HCV life cycle and suggest that the HCV core may be a valuable probe for host cell biology.
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, CCSR Building, Room 3115, 269 Campus Dr., Palo Alto, CA 94305-5187, USA.
Meirav
M
Matto
Charles M
CM
Rice
Benjamin
B
Aroeti
Jeffrey S
JS
Glenn
D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003505:Cyclodextrins / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology*; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D017830:Octoxynol / Q000494:pharmacology; D012093:Replicon; D014758:Viral Core Proteins / Q000378:metabolism*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D003902:Detergents; D014758:Viral Core Proteins; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D017830:Octoxynol