STAPHYLOCOCCAL SUPERANTIGENS ACTIVATE HIV-1 REPLICATION IN NATURALLY INFECTED MONOCYTES

Objectives: To study the effects of microbial superantigens, Staphyloc occal exotoxins (SE), on HIV replication in monocytes following bindin g to and signalling through major histocompatibility complex (MHC) cla ss II molecules. Methods: We investigated the effects of SE on HIV rep lication and monokine production in three different in vitro models of monocyte culture: chronically infected monocytic cell line U1, acute infection of normal monocytes by different HIV-1 strains, and naturall y-infected monocytes from seropositive patients. p24 antigen, interleu kin (IL)-6 and tumour necrosis factor (TNF)-alpha production was measu red by specific enzyme-linked immunosorbent assay (ELISA). Results: St aphylococcal enterotoxin B and toxic shock syndrome toxin-1 (1-1000 ng /ml) are powerful inducers of HIV-1 expression in U1 cells pretreated with granulocyte macrophage colony stimulating factor. SE induce viral replication in short-term cultures (days 6-21) of monocytes infected in vitro by HIVBa-L, HIVLAI, or naturally infected in vivo. Induction of HIV expression requires direct interactions of SE with MHC class II molecules but not T-cell receptor binding and T-cell-monocyte contact . Anti-TNF-alpha and anti-IL-6 neutralizing monoclonal antibodies inhi bit by over 61% SE-induced HIV replication. Conclusions: Using SE we h ave linked two important pathways For the regulation of HIV replicatio n in monocytes, namely signalling through MHC class II molecules and m onokine production potentially mediated by induction of the pleiotropi c cellular transcription factor NF-kappa B. In HIV-infected patients b acterial infections are common and could be an important cofactor in t he immunopathogenesis of AIDS by inducing HIV replication in latently infected monocytes. Their prevention might emerge as beneficial in the se patients.