The HIV-1 reservoir in distinct V beta subsets of CD4 T cells: evidence for a putative superantigen.

Human immunodeficiency virus-1 (HIV-1) replicates more efficiently in T cells expressing T-cell receptors using certain V beta genes, V beta 12 in particular. This V beta specificity was consistent with an HIV-1-associated superantigen. In addition, T cell-depleted peripheral blood mononuclear cells from HIV-positive donors potently stimulated V beta 12 cell lines to proliferate in culture, but not control B beta 6.7a cell lines, thus indicating the presence of a V beta-selective mitogen. The targeted V beta subsets were not deleted. It was therefore possible that these subsets might represent a viral reservoir in vivo. Viral load was assessed by quantitative polymerase chain reaction (with HIV-1 gag primers) and with an infectivity assay to measure competent virus. It was shown that the tiny V beta 12 subset (1-2% of T cells) has a higher viral load than other V beta subsets in about 65% of infected individuals. Selective HIV-1 replication in V beta 12 cells was also observed 6-9 days after in vitro infection of peripheral blood T cells from several normal HIV-1-negative donors. In summary, a superantigen-like activity appears to promote V beta-selective HIV-1 replication in vitro and in vivo in patients infected with HIV-1. New therapeutic approaches are suggested based on these findings.