| Texto completo | |
| Autor(es): Mostrar menos - |
de Sousa, Francielle T. G.
;
Warnes, Colin M.
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Manuli, Erika R.
;
Tjang, Laurentia V.
;
Carneiro, Pedro H.
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Pinto, Luzia Maria de Oliveira
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Ng, Arash
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Bhat, Samhita
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Zambrana, Jose Victor
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Zanella, Elia
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Ho, Yeh-Li
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Romano, Camila M.
;
Beatty, P. Robert
;
Biering, Scott B.
;
Kallas, Esper G.
;
Sabino, Ester C.
;
Harris, Eva
Número total de Autores: 17
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| Tipo de documento: | Artigo Científico |
| Fonte: | EBIOMEDICINE; v. 109, p. 15-pg., 2024-10-24. |
| Resumo | |
Background Yellow fever virus (YFV) infections are a major global disease concern with high mortality in humans, and as such it is critical to identify clinical correlates of disease severity. While nonstructural protein 1 (NS1) of the related dengue virus is implicated in contributing to vascular leak, little is known about the role of YFV NS1 in severe YF and mechanisms of vascular dysfunction in YFV infections. Methods Using serum samples from laboratory-confirmed YF patients with severe (n = 39) or non-severe (n = 18) disease in a well-defined hospital observational cohort in Brazil, plus samples from healthy uninfected controls (n = 11), we investigated factors associated with disease severity and endothelial dysfunction. Findings We found significantly increased levels of NS1, as well as syndecan-1, a marker of vascular leak, in serum from severe YF as compared to non-severe YF or control groups. We also showed that hyperpermeability of endothelial cell monolayers treated with serum from severe YF patients was significantly higher compared to non- severe YF and control groups, as measured by transendothelial electrical resistance (TEER). Further, we demonstrated that YFV NS1 induces shedding of syndecan-1 from the surface of human endothelial cells. Notably, YFV NS1 serum levels significantly correlated with syndecan-1 serum levels, TEER values, and signs of disease severity. Syndecan-1 levels also significantly correlated with clinical laboratory parameters of disease severity, viral load, hospitalization, and death. Interpretation This study provides further evidence for endothelial dysfunction as a mechanism of YF pathogenesis in humans and suggests serum quantification of YFV NS1 and syndecan-1 as valuable tools for disease diagnosis and/or prognosis. (AU) | |
| Processo FAPESP: | 13/01690-0 - Implantação de um modelo in vitro de avaliação da permeabilidade vascular para estudos da patogênese da dengue hemorrágica e triagem de compostos com potencial terapêutico |
| Beneficiário: | Ester Cerdeira Sabino |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 17/16627-3 - Avaliação dos efeitos das quimiocinas CXCL1 e CXCL10 e do potencial terapêutico de uma glucomanana sulfatada do Agaricus brasiliensis (MI-S) na dengue grave através de modelos in vitro e in vivo de extravasamento plasmático |
| Beneficiário: | Francielle Tramontini Gomes de Sousa |
| Modalidade de apoio: | Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado |
| Processo FAPESP: | 13/01702-9 - Avaliação da permeabilidade endotelial para estudos da patogênese da dengue e triagem de compostos com potencial terapêutico |
| Beneficiário: | Francielle Tramontini Gomes de Sousa |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |