MOLECULAR UNCOUPLING OF C-C CHEMOKINE RECEPTOR 5-INDUCED CHEMOTAXIS AND SIGNAL-TRANSDUCTION FROM HIV-1 CORECEPTOR ACTIVITY

The C-C chemokine receptor 5 (CCR5) plays a crucial role in facilitati ng the entry of macrophage-tropic strains of the HIV-1 into cells, but the mechanism of this phenomenon is completely unknown. To explore th e role of CCR5-derived signal transduction in viral entry, we introduc ed mutations into two cytoplasmic domains of CCR5 involved in receptor -mediated function, Truncation of the terminal carboxyl-tail to eight amino acids or mutation of the highly conserved aspartate-arginine-tyr osine, or DRY, sequence in the second cytoplasmic loop of CCR5 effecti vely blocked chemokine-dependent activation of classic second messenge rs, intracellular calcium fluxes, and the cellular response of chemota xis, In contrast, none of the mutations altered the ability of CCR5 to act as an HIV-1 coreceptor, We conclude that the initiation of signal transduction, the prototypic function of G protein coupled receptors, is not required for CCR5 to act as a coreceptor for HIV-1 entry into cells.