HIV and SIV gp120 binding does not predict coreceptor function

Interaction of HIV and SIV Envelope (Env) proteins with viral coreceptors i s a critical step in viral entry. By using a sensitive and specific gp120 b inding assay, we have identified a discordance between the ability of a cor eceptor to support Env-mediated membrane fusion and high-affinity binding o f gp120. Direct binding of gp120 from the dual-tropic HIV-1 strain 89.6 was not detectable for any coreceptor that it uses for fusion, while detectabl e binding of gp120s from the R5 HIV-1 strains JRFL and CM235 and the SIV st rain 239 was not measurable for many CCR5 chimeras and mutants that functio n efficiently as viral coreceptors. In comparison, binding of chemokines to these same mutants was highly predictive of their ability to signal. Thus, gp120 is more sensitive than chemokines to perturbations of CCR5 structure . We conclude that while chemokine binding to CCR5 is a good predictor of c hemokine receptor function, gp120 binding does not always predict corecepto r function. (C) 1999 Academic Press.