title: The roles of CD81 and glycosaminoglycans in the adsorption and uptake of infectious HCV particles.
abstract: Because appropriate cell-culture systems or small-animal models have been lacking, the early steps in the HCV life cycle have been difficult to study. A cell culture system was developed recently that allows production of infectious HCV. In this study, infectious HCV particles produced in cultured cells were used. To clarify the role of CD81 in HCV attachment and entry, the effect of anti-CD81 antibody was examined. The antibody blocked HCV virion entry but not particle attachment. Only the fraction bound to a heparin affinity column and eluted with 0.3 M NaCl productively infected Huh7 cells, indicating that infectious HCV particles bind to heparin. Both heparin treatment of the virus particles and heparinase treatment of the Huh7 cells reduced virus-cell binding without substantially inhibiting HCV infectivity. Finally, to confirm the role of both heparin sulfate proteoglycan (HSPG) and CD81 in HCV entry, the effects of heparinase I and anti-CD81 antibody were analyzed. No productive RNA replication was detected in the Huh7 cells in the presence of both heparinase I and anti-CD81 antibody. In conclusion, these data suggested that both HSPG and CD81 are important for HCV entry. HSPG may play a role in the initial cell surface binding of infectious HCV particles and CD81 is conceivably correlated with HCV entry after viral attachment.
authors: Department of Microbiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
authors: Kenichi
authors: K
authors: Morikawa
authors: Zijiang
authors: Z
authors: Zhao
authors: Tomoko
authors: T
authors: Date
authors: Michiko
authors: M
authors: Miyamoto
authors: Asako
authors: A
authors: Murayama
authors: Daisuke
authors: D
authors: Akazawa
authors: Junichi
authors: J
authors: Tanabe
authors: Saburo
authors: S
authors: Sone
authors: Takaji
authors: T
authors: Wakita
mesh_terms: D000906:Antibodies / Q000378:metabolism; D015703:Antigens, CD / Q000502:physiology*; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000502:physiology*; D006493:Heparin / Q000031:analogs & derivatives* / Q000378:metabolism; D019763:Heparin Lyase / Q000378:metabolism; D006801:Humans; D011509:Proteoglycans / Q000378:metabolism*; D012367:RNA, Viral / Q000096:biosynthesis; D011991:Receptors, Virus / Q000502:physiology*; D060225:Tetraspanin 28; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D000906:Antibodies; D015703:Antigens, CD; C554798:CD81 protein, human; D011509:Proteoglycans; D012367:RNA, Viral; D011991:Receptors, Virus; D060225:Tetraspanin 28; C036090:heparin proteoglycan; D006493:Heparin; D019763:Heparin Lyase