News Insights Into HIV Pathogenesis

New research into the distribution of chemokine receptors in the bodyhas provided clues to how HIV infection may progress to AIDS, according to researchers at Harvard Medical School, the University of Pennsylvania and LeukoSite Inc. The work is reported in the Proceedings of the National Academy of Sciences (March 4).

The two receptors under study, CCR5 and CXCR4 (also known as Lestr or fusin), were recently identified as coreceptors, along with CD4, for the entry of HIV into immune cells. The researchers used antibodies to map the distribution of the two receptors, and report that the CCR5 receptor is found mainly on memory T cells, while CXCR4 is found on naive cells.

This work follows studies which have demonstrated that HIV-1 strains have distinct cellular tropisms, ie they are either M-tropic (infecting macrophages and primary T cells), or T-tropic (able to infect primary T cells but not monocytes or macrophages). Last year, CXCR4 was found to allow entry of T-tropic strains into CD4 cells, while CCR5 was found to be the major coreceptor for M-tropic HIV-1. More recently, it has been suggested that a mutation in the CCR5 gene renders individuals resistant to HIV infection, which argues strongly that M-tropic strains are critical for establishing infection.