Roles of chemokines and chemokine receptors in HIV-1 infection

Abstract

Human immunodeficiency virus type 1 (HIV-1) uses a coreceptor together with CD4 to enter CD4+ target cells. The chemokine receptors CXCR4 and CCR5 have been found to be the major coreceptors for T-cell line-tropic and macrophage-tropic HIV-1 strains, respectively, although many other chemokine and orphan receptors have also been identified as potential coreceptors for HIV-1. Genetic analyses has revealed the importance of chemokine and chemokine receptor genes in disease progression. The discovery of coreceptors provides a more defined scheme for virus entry in which the HIV-1 envelope glycoprotein sequentially binds CD4 and coreceptor, leading to a membrane fusion reaction between the viral envelope and the plasma membrane of the target cell. It also provides the basis for HIV-1 cell tropism. The identification of HIV coreceptors provides new opportunities for the development of anti-HIV therapy. Many coreceptor-based therapeutic approaches have been developed, some of which are currently in clinical trials.