SUPERANTIGEN TOXIC SHOCK SYNDROME TOXIN-1 (TSST-1) ENHANCES THE REPLICATION OF HIV-1 IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS THROUGH SELECTIVE ACTIVATION OF CD4(-LYMPHOCYTES() T)

Staphylococcus aureus has been recognized as a common cause of bactere mia 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 t oxin-1 (TSST-1) brings about a high level of viral production in HIV-1 -infected peripheral blood mononuclear cells (PBMCs) through their act ivation in vitro. The p24 antigen level in the culture supernatant mar kedly increased in the presence of TSST-1 at a concentration of 1 pg/m l or higher. Fluorescent-activated cell sorter analysis revealed that TSST-1 specifically activated CD4(+) T lymphocytes. Although significa nt 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 identi fied in HIV-1 infected PBMCs with or without TSST-1 treatment. The add ition of anti-TNF-alpha antibody to the culture medium resulted in a d ramatic decrease in HIV-1 replication. These results suggest that the enhanced replication of HIV-1 by TSST-1 in PBMCs is attributable mainl y 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 pe r milliliter, the superantigen TSST-1 may play an important role in th e pathogenesis and clinical course of HIV-1 infections.