HIV-1 Tat Triggers TGF-β Production and NK Cell Apoptosis that is Prevented by Pertussis Toxin B. Issue 2 (2006)

• Record Type: Journal Article
• Authors: Poggi, Alessandro; Zocchi, Maria Raffaella
• Is Part Of: Clinical & developmental immunology. Volume 13:Issue 2/4(2006)
• Page Start: 369
• Page End: 372
• Publication Date: 2006
• Subjects: Developmental immunology -- Periodicals; Clinical immunology -- Periodicals; Immune System -- immunology -- Periodicals; Immune System -- growth & development -- Periodicals; Immune System Diseases -- immunology -- Periodicals; 571.9638
• DOI: 10.1080/17402520600645712
• Languages: English
• ISSNs: 1740-2522

Abstract

Abstract : Herein, we show that PTX-B and its non-toxic mutant PT9K/129G inhibit transcription and secretion of TGF-β elicited by HIV-1 Tat in NK cells. Moreover, Tat strongly activates the cJun component of the multimolecular complex AP-1, while TGF-β triggers cFos and cJun. Treatment of NK cells In turn, with PTX-B or PT9K/129G inhibits Tat and TGF-β-induced activation of AP-1. TGF-β enhances starvation-induced NK cell apoptosis, reduces the transcription of the antiapoptotic protein Bcl-2 and inhibits Akt phosphorylation induced by oligomerization of the triggering NK cell receptor NKG2D. All these TGF-β-mediated effects are prevented by PTX-B or PT9K/129G, through a PI-3K-dependent mechanism. Finally, PTX-B and PT9K/129G upregulate Bcl-xL, the isoform of Bcl-x that protects cells from starvation-induced apoptosis. Of note, in NK cells from patients with HIV-1 infection, mRNA expression of Bcl-2 and Bcl-xL was consistently lower than that of healthy donors; interestingly, TGF-β and Tat were detected in the sera of these patients. These data suggest that Tat-induced TGF-β production and the consequent NK cell failure, possibly occurring during early HIV-1 infection, may be regulated by PTX-B and PT9K/129G.