Staphylococcal Enterotoxin Superantigens Induce Prophylactic Antiviral Activity Against Encephalomyocarditis Virus In Vivo and In Vitro

The staphylococcal enterotoxins (SEs) are classified as superantigens due to their potent stimulation of the immune system resulting in T cell activation and prodigious cytokine production and toxicity. This study examined the ability of superantigens to induce prophylactic antiviral activity in vivo and in vitro and evaluated potential superantigen mimetic peptides. Prophylactic treatment of mice in vivo with intraperitoneal injections of SE superantigens SEA and SEB (both at 20 mu g/day for 3 days) prevented encephalomyocarditis virus (EMCV)-induced lethality in 100% and 80% of mice, respectively, as compared with control saline-treated groups in which EMCV was lethal to all mice. Furthermore, SEA (2 mu g/mL) and SEB (1 mu g/mL) induced antiviral activity in mouse splenocytes to produce an antiviral factor since their supernatant prevented EMCV lysis of L929 cells in tissue culture. It was found that superantigens do not directly prevent EMCV infection, but rather indirectly through inducing interferon gamma (IFN gamma) production in cells as the antiviral factor. Evaluation of various superantigen mimetic peptides showed that one peptide (SEA3) had superantigen-like activity by inducing IFN gamma production in cells but without the cellular proliferation, as associated with superantigens. However, the induction of IFN gamma activation by the SEA3 peptide was not as pronounced, and took a much higher peptide concentration, when compared with the parent superantigen. If the negative side effects of superantigens can be eliminated, their beneficial properties can be harnessed for prophylactic treatment of viral infections and other pathologies requiring a robust immune response.

Automated summary

Staphylococcal enterotoxins, classified as superantigens, have potent immune activation and antiviral activity by inducing interferon gamma production. These superantigens could potentially be used for prophylactic treatment of viral infections and other pathologies requiring a robust immune response if their negative side effects can be eliminated.