A potential role of the heparan sulfate in the hepatitis C virus attachment.
Several putative cell surface receptors have been identified in the Hepatitis C virus (HCV) infection including CD81, low-density lipoprotein (LDL) receptor, scavenger receptor class B type I (SR-BI), and highly sulfated heparan sulfate (HS). In this study, we showed that the binding of soluble heparin to the envelope glycoprotein E2 (E2) of HCV was dependent on the dose and conformation of E2. On the other hand, the binding of E2 to the cell surface after treatment with soluble heparin was not markedly inhibited, what was different from other viruses utilizing cellular HS as the primary receptor. However, the enzymatic removal of HS from the cell surface led to a significant reduction in the binding of E2 to the cells. These facts imply that E2 was bound to cellular HS but might also have another route for cell attachment. Monoclonal antibodies with neutralizing activity against E2 did not completely block the binding of E2 to the cell surface, but their neutralization activity was greatly enhanced in the presence of soluble heparin. Taken together, the cellular HS could act as an alternative receptor for HCV and the interaction of E2 with HS could play a distinct role in escaping of HCV from the humoral immunity.
Heo
T H
TH
Department of Biomedical Laboratory Science, Konyang University, Daejeon, 320-718, Korea. thhur92@konyang.ac.kr
D002460:Cell Line; D016174:Hepacivirus / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism*; D006526:Hepatitis C / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D053585:Virus Attachment
D006497:Heparan Sulfate; D011991:Receptors, Virus; D014759:Viral Envelope Proteins