O-sulfate groups of heparin are critical for inhibition of ecotropic murine leukemia virus infection by heparin

There is increasing evidence that soluble glycosaminoglycans such as heparin can interfere with the infectivity of various viruses, including ecotropic murine leukemia viruses (MLVs). The ecotropic MLV, Friend MLV (F-MLV) and the neuropathogenic variants A8 MLV and PVC-211 MLV, were susceptible to heparin-mediated inhibition of infection of NIH 3T3 cells. To investigate the interaction between the envelope glycoprotein (Env) of MLV and heparin, we prepared vesicular stomatitis virus-based pseudotyped viruses carrying the Env of F-, A8, or PVC-211 MLVs. Surface plasmon resonance analyses indicated that the Env of A8 and PVC-211 MLVs had a higher binding activity to heparin than that of F-MLV. We examined the influence of N- or O-sulfation of heparin on binding activity to Env and on the inhibition of the infectivity of MLV and pseudotyped viruses carrying Env. This analysis indicated that the O-sulfate groups of heparin play a major role in determining Env-dependent inhibitory effects.