Hypersensitivity of HIV-1-Infected Cells to Reactive Sulfonamide Metabolites Correlated to Expression of the HIV-1 Viral Protein Tat

Arp, Jacqueline; Rieder, Michael J.; Urquhart, Brad L.; Freeman, David J.; Tucker, M. J.; Krizova, Adriana; Lehmann, David F.; Dekaban, Gregory A.

doi:10.1124/jpet.105.085050

Cited by 20 publications

(50 citation statements)

References 37 publications

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Section: Discussioncontrasting

confidence: 56%

“…Indeed, this toxicity was the basis for an in vitro model of hypersensitivity ADRs as peripheral blood lymphocytes from patients with a history of hypersensitivity ADRs showed significantly increased toxicity across a concentration range of SMX-HA compared to those from controls and patients with a history of non-hypersensitivity reactions [6]. A similar finding was reported in HIV-1-positive patients where SMX-HA cytotoxicity was greater in patients known to exhibit hypersensitivity ADRs [7] and, as we previously demonstrated, also correlated with HIV-1 infection in established T cell lines and with the expression of recombinant HIV-1 Tat (Transactivator of transcription) protein in T cell lines [4,8].…”

Section: Introductionsupporting

confidence: 66%

“…ADRs to SMX in patients undergoing antiretroviral therapy arise increasingly as HIV-1 infection progresses to AIDS suggesting that HIV-1 is a key contributing factor. Previously, our research has shown that the HIV-1 Tat protein is such a factor as Tat expression correlates with increased sensitivity to SMX-HA, the reactive metabolite of SMX [8,21]. In this study we sought to determine the region of the Tat protein mediating this effect.…”

Section: Discussionmentioning

confidence: 99%

“…The differential expression of Tat also had a cooperative effect on SMX-HA-mediated toxicity, significantly decreasing cell viability further as the expression of the TatGFP protein was increased [8]. The failure of Tat72GFP expression in this paper to potentiate SMX-HA-mediated cell death is in contrast to previously published data [8,21]. This may be due to the fact that the sequence of the 72 amino acid Tat protein used in the aforementioned publications (TatGFP) differs by eleven amino acids from the Tat protein used in the current study (Tat72GFP).…”

Section: Discussionmentioning

confidence: 99%

“…Our studies have also shown that this effect on viability is amplified in the presence of the Tat protein and is also influenced by the amount of Tat protein in the cell [8]. The Tat-expressing cell lines were used to determine the region or domain of the protein that is involved in enhancing toxicity.…”

Section: Cell Viability Of Tat-expressing Cell Lines After Treatment mentioning

confidence: 99%

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

Adeyanju¹,

Dekaban²,

Rieder³

2016

HIV Curr Res

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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.

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Section: Discussioncontrasting

confidence: 56%

Section: Introductionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cell Viability Of Tat-expressing Cell Lines After Treatment mentioning

confidence: 99%

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

Adeyanju¹,

Dekaban²,

Rieder³

2016

HIV Curr Res

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HIV Tat potentiates cell toxicity in a T cell model for sulphamethoxazole-induced adverse drug reactions

et al. 2009

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HIV infection results in severe immune dysfunction with ensuing sequelae that includes characteristic opportunistic infections. Pneumocystis pneumonia (PCP) is one of the most common of these infections and is routinely treated with sulphamethaxazole (SMX). Although this drug is known to cause hypersensitivity adverse drug reactions (ADRs) in 0.1% of the general population, the incidence of these ADRs increases tenfold in the HIV-positive population. The HIV-1 trans-activator of transcription (HIV-1 Tat) together with the drug metabolite sulphamethaxazole-hydroxylamine (SMX-HA) have both been reported to be factors in these hypersensitivity ADRs. In this study, we use an inducible, Tat-expressing vector system to show that the level of Tat expression contributes to the cellular sensitivity of Jurkat T cells to SMX-HA. We further demonstrated that apoptosis is the likely mechanism by which this occurs. Thus, our data provide insight into the significant increase of SMX-related ADRs during the transition between HIV-1 infection and AIDS.

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Sulfonamide Hypersensitivity

Chow

Khan

2021

Clinic Rev Allerg Immunol

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Hypersensitivity of HIV-1-Infected Cells to Reactive Sulfonamide Metabolites Correlated to Expression of the HIV-1 Viral Protein Tat

Cited by 20 publications

References 37 publications

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

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

HIV Tat potentiates cell toxicity in a T cell model for sulphamethoxazole-induced adverse drug reactions

Sulfonamide Hypersensitivity

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