The Good, the Bad, and the Shocking: The Multiple Roles of Dengue Virus Nonstructural Protein 1 in Protection and Pathogenesis

Dengue virus (DENV) is the most prevalent medically important mosquito-borne virus in the world. Upon DENV infection of a host cell, DENV nonstructural protein 1 (NS1) can be found intracellularly as a monomer, associated with the cell surface as a dimer, and secreted as a hexamer into the bloodstre...

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Bibliographic Details
Published in:Annual review of virology 2018-09, Vol.5 (1), p.227-253
Main Authors: Glasner, Dustin R, Puerta-Guardo, Henry, Beatty, P. Robert, Harris, Eva
Format: Article
Language:English
Subjects:
Cytokines - metabolism
dengue
Dengue - immunology
Dengue - prevention & control
Dengue - virology
Dengue Vaccines - immunology
Dengue Vaccines - isolation & purification
Dengue Virus - immunology
Dengue Virus - pathogenicity
Dengue Virus - physiology
endothelial permeability
Endothelium, Vascular - physiology
Endothelium, Vascular - virology
Host-Pathogen Interactions
Immune Evasion
NS1
Permeability
RNA, Viral - metabolism
vaccines
vascular leak
Viral Nonstructural Proteins - immunology
Viral Nonstructural Proteins - metabolism
Virus Replication
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Summary:Dengue virus (DENV) is the most prevalent medically important mosquito-borne virus in the world. Upon DENV infection of a host cell, DENV nonstructural protein 1 (NS1) can be found intracellularly as a monomer, associated with the cell surface as a dimer, and secreted as a hexamer into the bloodstream. NS1 plays a variety of roles in the viral life cycle, particularly in RNA replication and immune evasion of the complement pathway. Over the past several years, key roles for NS1 in the pathogenesis of severe dengue disease have emerged, including direct action of the protein on the vascular endothelium and triggering release of vasoactive cytokines from immune cells, both of which result in endothelial hyperpermeability and vascular leak. Importantly, the adaptive immune response generates a robust response against NS1, and its potential contribution to dengue vaccines is also discussed.
ISSN:2327-056X
2327-0578
DOI:10.1146/annurev-virology-101416-041848