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.
Hashimoto
K
K
Department of Microbiology, Fukushima Medical College, Japan.
Shigeta
S
S
Baba
M
M
D000906:Antibodies / Q000276:immunology; D001427:Bacterial Toxins; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004768:Enterotoxins / Q000494:pharmacology*; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D013211:Staphylococcus aureus; D018089:Superantigens / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology
D000906:Antibodies; D001427:Bacterial Toxins; D015704:CD4 Antigens; D016827:CD8 Antigens; D004768:Enterotoxins; D016655:HIV Core Protein p24; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal