Subversion of chemokine receptors by HIV: how can we exploit this?
The recent discovery that the chemokines RANTES (regulated upon activation, normal T-cell-expressed and secreted), macrophage inflammatory protein-1alpha (MIP-1a), and macrophage inflammatory protein-1beta (MIP-1b) are important modulators of HIV-1 infection and the subsequent identification of the essential role that chemokine receptors play as co-receptors for HIV-1 infection have provided new insight into the pathogenesis of HIV-1. On May 10, 1996, Ed Berger's group of the NIH announced the identity of one of the elusive ;co-receptors' for HIV-1. This, and subsequent papers showing that the expression of specific seven transmembrane (7TM) chemokine receptors and CD4 confers susceptibility to infection by HIV-1, has led to rapid and exciting advances in both chemokine and HIV research. During the year since then, a number of elegant studies by different groups have identified additional co-receptors for HIV-1 and the receptor involved in HIV-2 infection, as well as extended our understanding of the mechanism HIV utilises to enter cells. A number of researchers at academic institutes, pharmaceutical and biotech companies are gambling that this will translate into new therapeutics for the treatment of HIV infection and AIDS.
Pakianathan
D R
DR
Genentech, Inc., Immunology Department, South San Francisco, CA 94080, USA. deepa@gene.com