ROLE OF THE V2, V3, AND CD4-BINDING DOMAINS OF GP120 IN CURDLAN SULFATE NEUTRALIZATION SENSITIVITY OF HIV-1 DURING INFECTION OF T-LYMPHOCYTES

A sulfated polysaccharide, curdlan sulfate (CRDS) with 1,3-beta-D-gluc an as a main chain, inhibits HIV-1 infection of human peripheral blood lymphocytes (PBLs) by binding to the V3 region of gp120. We previousl y showed that T cell (T)-tropic HIV-1 isolates are over 10-fold more s ensitive to neutralization by CRDS than macrophage (MT)-tropic viruses , which posseses a relatively less charged amino acid composition in t he vs sequence. To analyze the interaction of CRDS with V3 and its ass ociation with neutralization sensitivity or HIV-1 isolates, we examine d the effect or CRDS on the binding of neutralizing antibodies to mono meric and oligomeric gp120 mutants of T- and MT-tropic HIV-I clones in which the V3 loop was either deleted or substituted by V3 of another isolate. Our results showed that the presence and the amino acid compo sition of the V3 loop appears to determine the extent of interaction o f CRDS with the V2 and CD4-binding regions on native gp120 monomers; h owever, the positive charge of vs has less effect on this interaction on oligomeric gp120. Furthermore, our results established that only th e CRDS-induced masking of V3 on oligomeric gp120 appears to be associa ted with the anti-HIV-1 activity of CRDS in vitro. Our findings underl ine the usefulnes of CRDS for understanding the structural constraints on gp120 that drive the transition from MT- to T-tropic isolates in v ivo and enable the Virus to use multiple fusion cofactors. (C) 1996 Ac ademic Press, Inc.