G-PROTEIN-COUPLED RECEPTORS IN HIV AND SIV ENTRY - NEW PERSPECTIVES ON LENTIVIRUS-HOST INTERACTIONS AND ON THE UTILITY OF ANIMAL-MODELS

Entry of primate lentiviruses into target cells has recently been show n to depend upon, the interaction of the viral envelope glycoprotein w ith CD4 and one or more members of the G protein-coupled receptor (GPC R) family of transmembrane proteins. In vivo, the transmission of HIV- 1 infection generally requires viral strains that utilise chemokine re ceptor CCR5, and these strains prevail during the early course of infe ction. Strains isolated later, in the course of progression to immunod eficiency, are often CXCR4-tropic or are dual tropic for both chemokin e receptors. SN isolates also use CCR5 but are only rarely specific fo r CXCR4. Instead, SIVs use two orphan members of the GPCR family, name d Bonzo/STRL33/TYMSTR and BOB/GPR15. Strains of HIV-5 which are closel y related to the SIVs, also often utilise CXCR4, CCR5, BOB and/or Bonz o. Additional GPCR family members have also been shown to be utilised by various strains of HIV and SIV albeit less efficiently and less fre quently. Here we discuss the potential relationship between receptor s pecificity and viral pathogenesis as well as efforts to develop animal model systems to study the mechanism of disease progression.