Cytoplasmic Distribution of HIV-1 Tat Sensitizes Jurkat T cells to Sulphamethoxazole-Hydroxylamine Induced Toxicity

Abstract

Background: One medication commonly used by HIV-1-infected individuals is the antimicrobial sulphamethoxazole (SMX), which is used in the treatment and prophylaxis of pneumocystis pneumonia. However, SMX is responsible for a very high incidence of hypersensitivity adverse drug reactions (ADRs) in the HIV-1 population. While the pathophysiology of ADRs in general is unknown, sulphamethoxazole-mediated ADRs have been linked to its reactive metabolite sulphamethoxazole-hydroxylamine (SMX-HA). Our previous work has shown that increased expression of the HIV-1 Tat protein in T cells correlated with increased apoptosis after incubation with SMX-HA. In this study we sought to determine the region of the Tat protein responsible for this effect and the mechanism by which Tat contributed to SMX-HA mediated apoptosis.