Superantigen toxic shock syndrome toxin-1 (TSST-1) enhances the replication of HIV-1 in peripheral blood mononuclear cells through selective activation of CD4+ T lymphocytes.

Staphylococcus aureus has been recognized as a common cause of bacteremia of such infections in human immunodeficiency virus type 1 (HIV-1)-seropositive patients. Some staphylococcal exotoxins are recognized as superantigens. We have found that superantigen toxic shock syndrome toxin-1 (TSST-1) brings about a high level of viral production in HIV-1-infected peripheral blood mononuclear cells (PBMCs) through their activation in vitro. The p24 antigen level in the culture supernatant markedly increased in the presence of TSST-1 at a concentration of 1 pg/ml or higher. Fluorescent-activated cell sorter analysis revealed that TSST-1 specifically activated CD4+ T lymphocytes. Although significant production of tumor necrosis factor alpha (TNF-alpha) was observed in uninfected PBMCs treated with TSST-1 after 96 h of incubation, much earlier (after 12 h of incubation) production of TNF-alpha was identified in HIV-1 infected PBMCs with or without TSST-1 treatment. The addition of anti-TNF-alpha antibody to the culture medium resulted in a dramatic decrease in HIV-1 replication. These results suggest that the enhanced replication of HIV-1 by TSST-1 in PBMCs is attributable mainly to the activation of CD4+ T lymphocytes and that the induction of TNF-alpha further enhances replication. Since the enhancement of HIV-1 replication by TSST-1 occurs in a concentration range of picograms per milliliter, the superantigen TSST-1 may play an important role in the pathogenesis and clinical course of HIV-1 infections.