Chemokine control of HIV-1 infection

Chemokines are proinflammatory cytokines that attract and activate specific types of leukocyte1. There are two main chemokine families, based on the position of the first two cysteine residues: the CC and the CXC chemokines1. Chemokines mediate their effects through interactions with seven-transmembrane-spanning glyco-protein receptors coupled to a G-protein signalling pathway1. Chemokine receptors normally undergo a ligand-mediated homodimerization process, which is required for Ca2+ flux and chemotaxis2. Here we show that in the chemokine response it is possible for heterodimerization, rather than homodimerization, to occur between a mutant form of the CCR2 receptor (the CCR2V64I receptor), which helps to delay the development of AIDS in HIV-1-infected individuals, and the CCR5 or CXCR4 chemokine receptor, which are used by HIV to gain entry into cells. These results may explain why AIDS takes longer to develop in HIV-1-infected individuals carrying the CCR2V64I mutation3.