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1.
J Infect Dis ; 222(9): 1488-1497, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32436943

RESUMO

BACKGROUND: Ebola virus (EBOV) disease has killed thousands of West and Central Africans over the past several decades. Many who survive the acute disease later experience post-Ebola syndrome, a constellation of symptoms whose causative pathogenesis is unclear. METHODS: We investigated EBOV-specific CD8+ and CD4+ T-cell responses in 37 Sierra Leonean EBOV disease survivors with (n = 19) or without (n = 18) sequelae of arthralgia and ocular symptoms. Peripheral blood mononuclear cells were infected with recombinant vesicular stomatitis virus encoding EBOV antigens. We also studied the presence of EBOV-specific immunoglobulin G, antinuclear antibodies, anti-cyclic citrullinated peptide antibodies, rheumatoid factor, complement levels, and cytokine levels in these 2 groups. RESULTS: Survivors with sequelae had a significantly higher EBOV-specific CD8+ and CD4+ T-cell response. No differences in EBOV-specific immunoglobulin G, antinuclear antibody, or anti-cyclic citrullinated peptide antibody levels were found. Survivors with sequelae showed significantly higher rheumatoid factor levels. CONCLUSION: EBOV-specific CD8+ and CD4+ T-cell responses were significantly higher in Ebola survivors with post-Ebola syndrome. These findings suggest that pathogenesis may occur as an immune-mediated disease via virus-specific T-cell immune response or that persistent antigen exposure leads to increased and sustained T-cell responses.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Ebolavirus/imunologia , Doença pelo Vírus Ebola/imunologia , Adulto , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Feminino , Imunofluorescência , Doença pelo Vírus Ebola/patologia , Humanos , Imunidade Celular , Masculino , Serra Leoa/epidemiologia , Sobreviventes
2.
Chem Res Toxicol ; 33(2): 678-686, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-31977195

RESUMO

Hydropersulfide and polysulfide species have recently been shown to elicit a wide variety of biological and physiological responses. In this study, we examine the effects of cysteine trisulfide (Cys-SSS-Cys; also known as thiocystine) treatment on E. coli. Previous studies in mammalian cells have shown that Cys-SSS-Cys treatment results in protection from the electrophiles. Here, we show that the protective effect of Cys-SSS-Cys treatment against electrophile-induced cell death is conserved in E. coli. This protection correlates with the rapid generation of cysteine hydropersulfide (Cys-SSH) in the culture media. We go on to demonstrate that an exogenous phosphatase expressed in E. coli, containing only a single catalytic cysteine, is protected from electrophile-induced inactivation in the presence of hydropersulfides. These data together demonstrate that E. coli can utilize Cys-SSS-Cys to generate Cys-SSH and that the Cys-SSH can protect cellular thiols from reactivity with the electrophiles.


Assuntos
Cistina/farmacologia , Escherichia coli/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Sulfetos/farmacologia , Cistina/análogos & derivados , Cistina/química , Escherichia coli/citologia , Escherichia coli/metabolismo , Sulfetos/química , Sulfetos/metabolismo
3.
Chem Res Toxicol ; 32(3): 447-455, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30681327

RESUMO

Hydropersulfides and related polysulfides have recently become topics of significant interest due to their physiological prevalence and proposed biological functions. Currently, examination of the effects of hydropersulfide treatment on cells is difficult due to their lack of inherent stability with respect to disproportionation. Herein, it is reported that the treatment of a variety of cell types with cysteine trisulfide (also known as thiocystine; Cys-SSS-Cys), results in an increase in intracellular hydropersulfide levels (e.g., cysteine hydropersulfide; Cys-SSH, and glutathione hydropersulfide; GSSH). Thus, Cys-SSS-Cys represents a possible pharmacological agent for examining the effects of hydropersulfides on cell function/viability. It has also been found that cells with increased intracellular hydropersulfide levels can export Cys-SSH into the extracellular media. Interestingly, the Cys-SSH is the major hydropersulfide exported by cells, although GSSH is the predominant intracellular species. The possible implications of cellular export are discussed.


Assuntos
Cisteína/metabolismo , Cisteína/toxicidade , Sulfetos/metabolismo , Sulfetos/toxicidade , Células 3T3 , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cisteína/química , Humanos , Camundongos , Estrutura Molecular , Sulfetos/química , Sais de Tetrazólio/farmacologia
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