Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1Research in context
Summary: 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...
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Elsevier
2024-11-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396424004456 |
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| author | Francielle T.G. de Sousa Colin M. Warnes Erika R. Manuli Laurentia V. Tjang Pedro H. Carneiro Luzia Maria de Oliveira Pinto Arash Ng Samhita Bhat Jose Victor Zambrana Luiz G.F.A.B. D’Elia Zanella Yeh-Li Ho Camila M. Romano P. Robert Beatty Scott B. Biering Esper G. Kallas Ester C. Sabino Eva Harris |
| author_facet | Francielle T.G. de Sousa Colin M. Warnes Erika R. Manuli Laurentia V. Tjang Pedro H. Carneiro Luzia Maria de Oliveira Pinto Arash Ng Samhita Bhat Jose Victor Zambrana Luiz G.F.A.B. D’Elia Zanella Yeh-Li Ho Camila M. Romano P. Robert Beatty Scott B. Biering Esper G. Kallas Ester C. Sabino Eva Harris |
| author_sort | Francielle T.G. de Sousa |
| collection | DOAJ |
| description | Summary: 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. Funding: This work was supported by the US NIH and FAPESP. |
| format | Article |
| id | doaj-art-3b8a23f7c7c749fdb3a1dbe8142a44c7 |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
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| series | EBioMedicine |
| spelling | doaj-art-3b8a23f7c7c749fdb3a1dbe8142a44c72024-11-14T04:32:25ZengElsevierEBioMedicine2352-39642024-11-01109105409Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1Research in contextFrancielle T.G. de Sousa0Colin M. Warnes1Erika R. Manuli2Laurentia V. Tjang3Pedro H. Carneiro4Luzia Maria de Oliveira Pinto5Arash Ng6Samhita Bhat7Jose Victor Zambrana8Luiz G.F.A.B. D’Elia Zanella9Yeh-Li Ho10Camila M. Romano11P. Robert Beatty12Scott B. Biering13Esper G. Kallas14Ester C. Sabino15Eva Harris16Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA; Departamento de Doenças Infecciosas e Parasitárias, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 05403000, Brazil; Laboratório de Investigação Médica, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP 05403000, BrazilDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USADepartamento de Doenças Infecciosas e Parasitárias, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 05403000, Brazil; Laboratório de Investigação Médica, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP 05403000, BrazilDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USADivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USADivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA; Laboratório das Interações Vírus-Hospedeiros (LIVH), Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (IOC/Fiocruz), Rio de Janeiro 21040-360, BrazilDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, 94720-3200, USADivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USADepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USAHospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP 05403000, BrazilHospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP 05403000, BrazilDepartamento de Doenças Infecciosas e Parasitárias, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 05403000, Brazil; Laboratório de Investigação Médica, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP 05403000, BrazilDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA; Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, 94720-3200, USADivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USADepartamento de Doenças Infecciosas e Parasitárias, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 05403000, Brazil; Laboratório de Investigação Médica, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP 05403000, Brazil; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP 05403000, BrazilDepartamento de Doenças Infecciosas e Parasitárias, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 05403000, Brazil; Laboratório de Investigação Médica, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP 05403000, Brazil; Corresponding author. Departamento de Doenças Infecciosas e Parasitárias, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP 05403000, Brazil.Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA; Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, 94720-3200, USA; Corresponding author. Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA.Summary: 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. Funding: This work was supported by the US NIH and FAPESP.http://www.sciencedirect.com/science/article/pii/S2352396424004456Yellow feverPathogenesisEndothelial dysfunctionNS1Syndecan-1 |
| spellingShingle | Francielle T.G. de Sousa Colin M. Warnes Erika R. Manuli Laurentia V. Tjang Pedro H. Carneiro Luzia Maria de Oliveira Pinto Arash Ng Samhita Bhat Jose Victor Zambrana Luiz G.F.A.B. D’Elia Zanella Yeh-Li Ho Camila M. Romano P. Robert Beatty Scott B. Biering Esper G. Kallas Ester C. Sabino Eva Harris Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1Research in context EBioMedicine Yellow fever Pathogenesis Endothelial dysfunction NS1 Syndecan-1 |
| title | Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1Research in context |
| title_full | Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1Research in context |
| title_fullStr | Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1Research in context |
| title_full_unstemmed | Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1Research in context |
| title_short | Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1Research in context |
| title_sort | yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral ns1 protein and syndecan 1research in context |
| topic | Yellow fever Pathogenesis Endothelial dysfunction NS1 Syndecan-1 |
| url | http://www.sciencedirect.com/science/article/pii/S2352396424004456 |
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