Cellular Binding of Hepatitis C Virus Envelope Glycoprotein E2

The conservation of positively charged residues in the N terminus of the hepatitis C virus (HCV) envelope gly-coprotein E2 suggests an interaction of the viral enve-lope with cell surface glycosaminoglycans. Using recom-binant envelope glycoprotein E2 and virus-like particles as ligands for cellular binding, we demonstrate that cell surface heparan sulfate proteoglycans (HSPG) play an important role in mediating HCV envelope-target cell interaction. Heparin and liver-derived highly sulfated heparan sulfate but not other soluble glycosaminogly-cans inhibited cellular binding and entry of virus-like particles in a dose-dependent manner. Degradation of cell surface heparan sulfate by pretreatment with hepa-rinases resulted in a marked reduction of viral envelope protein binding. Surface plasmon resonance analysi