Chemokines and HIV infection

The recent collision between two previously distant worlds, chemokines and AIDS, has prompted an extraordinary leap forward in our understanding of some fundamental aspects of the physiology of HIV infection, which had remained elusive for more than a decade. After the identification of the C-C chemokines regulated on activation normal T-cell expressed and secreted, macrophage inflammatory protein-1 alpha and macrophage inflammatory protein-1 beta as major components of the HIV-suppressive activity produced by CD8+ T lymphocytes, several chemokine receptors, in particular CXCR4 and CCR5, were shown to serve as co-receptors for HIV on the cellular surface membrane. The differential usage of such coreceptors, that is critically dependent on the sequence of the V3 domain of the major viral envelope glycoprotein, gp120, is emerging as the physiological basis for the diversity among the HIV isolates recovered at different stages of the disease. Moreover, a homozygous deletion within the coding sequence of the CCR5 gene has been linked to resistance to HIV infection in some individuals with multiple high-risk sexual exposure. The rapid progress in this field may ultimately lead to the development of novel therapeutic approaches for AIDS.