Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1

de Sousa, Francielle T.G.; Warnes, Colin M.; Manuli, Erika R.; Tjang, Laurentia V.; Carneiro, Pedro H.; Maria de Oliveira Pinto, Luzia; Ng, Arash; Bhat, Samhita; Zambrana, Jose Victor; D’Elia Zanella, Luiz G.F.A.B.; Ho, Yeh-Li; Romano, Camila M.; Beatty, P. Robert; Biering, Scott B.; Kallas, Esper G.; Sabino, Ester C.; Harris, Eva

doi:10.1016/j.ebiom.2024.105409

eBioMedicine

2024

DOI: 10.1016/j.ebiom.2024.105409

|View full text |Cite

Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1

Francielle T.G. de Sousa,

Colin M. Warnes,

Erika R. Manuli

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Preprint1

Relationship

Self Cite0

Independent1

Authors

Journals

Cited by 1 publication

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Flavivirus NS1-triggered endothelial dysfunction promotes virus dissemination

Puerta-Guardo,

Biering,

Castillo-Rojas

et al. 2024

Preprint

View full text Add to dashboard Cite

The Flaviviridae are a family of viruses that include the important arthropod-borne human pathogens dengue virus (DENV), West Nile virus, Zika virus, Japanese encephalitis virus, and yellow fever virus. Flavivirus nonstructural protein 1 (NS1) is essential for virus replication but is also secreted from virus-infected cells. Extracellular NS1 acts as a virulence factor during flavivirus infection in multiple ways, including triggering endothelial dysfunction and vascular leak via interaction with endothelial cells. While the role of NS1 in inducing vascular leak and exacerbating pathogenesis is well appreciated, if and how NS1-triggered endothelial dysfunction promotes virus infection remains obscure. Flaviviruses have a common need to disseminate from circulation into specific tissues where virus-permissive cells reside. Tissue-specific dissemination is associated with disease manifestations of a given flavivirus, but mechanisms dictating virus dissemination are unclear. Here we show that NS1-mediated endothelial dysfunction promotes virus dissemination in vitro and in vivo. In mouse models of DENV infection, we show that anti-NS1 antibodies decrease virus dissemination, while the addition of exogenous NS1 promotes virus dissemination. Using an in vitro system, we show that NS1 promotes virus dissemination in two distinct ways: (1) promoting crossing of barriers and (2) increasing infectivity of target cells in a tissue- and virus-specific manner. The capacity of NS1 to modulate infectivity correlates with a physical association between virions and NS1, suggesting a potential NS1-virion interaction. Taken together, our study indicates that flavivirus NS1 promotes virus dissemination across endothelial barriers, providing an evolutionary basis for virus-triggered vascular leak.

show abstract

Flavivirus NS1-triggered endothelial dysfunction promotes virus dissemination

Puerta-Guardo,

Biering,

Castillo-Rojas

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Yellow fever disease severity and endothelial dysfunction are associated with elevated serum levels of viral NS1 protein and syndecan-1

Cited by 1 publication

References 42 publications

Flavivirus NS1-triggered endothelial dysfunction promotes virus dissemination

Flavivirus NS1-triggered endothelial dysfunction promotes virus dissemination

Contact Info

Product

Resources

About