Chemokine Receptors: Keys to AIDS Pathogenesis?

Only two years ago, the rapidly expanding families of chemokines and of their seven-transmembrane G protein–coupled receptors (GPCRs) occupied an important, but not widely recognized, area of biology (reviewed inPremack and Schall 1996). The discoveries that chemokines can block HIV replication and that their receptors have essential functions in fusion of HIV to target cells propelled this field into the limelight, and raised expectations that chemokines might hold the key to understanding HIV-mediated pathogenesis, both in the immune system and the central nervous system. Although this promise has yet to be fulfilled, much has been learned since the early exciting findings, and it is now possible to formulate questions with considerably greater clarity. This review will focus on some recent advances and on outstanding questions regarding the role of chemokine receptor family members in the primate lentiviral replication cycle and in pathogenesis.