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NS1: A corner piece in the dengue pathogenesis puzzle?

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WRAIR Deputy Commander, COL Stephen Thomas, recently authored an editorial in Science Translational Medicine on the work of Beatty et al. regarding dengue virus NS1 protein. See below for excerpts and the full editorial:

“Dengue virus infection is a rapidly expanding public health problem of the tropics and subtropics. Population growth and expansion of habitats for the virus-carrying vector—the Aedes mosquito—coupled with the ease of international travel have aligned, in space and time, populations of dengue-susceptible hosts (humans) with circulating dengue viruses (DENVs) and the mosquitoes that transmit them. The result is hundreds of millions of infections each year, with nearly 100 million resulting in clinical phenotypes that cause human suffering and consumption of limited health care resources.

In endemic regions, most dengue disease can be and is successfully managed in an outpatient setting. Severe dengue can be deadly, requiring admission to hospital and advanced medical care upon diagnosis.

Not only is there no licensed vaccine to prevent dengue infection or specific antiviral or anti-inflammatory therapeutics to treat the disease, we also lack a complete understanding of the pathological processes that direct one infection toward a mild clinical presentation and another toward severe disease and possibly death. This has been a puzzle to stymied clinicians, basic scientists, dengue vaccine and drug developers and epidemiologists alike for decades.”

The editorial by COL Stephen Thomas covers the dengue pathogenesis puzzle explored by Modhiran et al. globe4.gif (2) and Beatty et al. globe4.gif (1) described in their results of in vitro and in vivo experiments, suggesting a central role for circulating dengue virus nonstructural protein 1.

Full editorial: http://stm.sciencemag.org/content/7/304/304fs37.full  globe4.gif

1. P. R. Beatty, H. Puerta-Guardo, S. S. Killingbeck, D. R. Glasner, K. Hopkins, E. Harris, Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination. Sci. Transl. Med. 7, 304ra141 (2015)

2. N. Modhiran, D. Watterson, D. A. Muller, A. K. Panetta, D. P. Sester, L. Liu, D. A. Hume, K. J. Stacey, P. R. Young, Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity. Sci. Transl. Med. 7, 304ra142 (2015)

 

Photo from Science Translational Medicine 9 September 2015 online publication:

ONLINE COVER You Give Me Fever. As suggested by its floating structure illustration, dengue virus nonstructural protein 1 (NS1) may take center stage in the battle against dengue hemorrhagic fever, according to a pair of studies in this week's issue. The life-threatening syndrome is characterized by cytokine storm, vascular leak, and toxic shock. Modhiran et al globe4.gif and Beatty et al globe4.gif have pinpointed NS1 as a driver of vascular leak via the innate immune Toll-like receptor 4, transforming NS1 into a probable therapeutic target and vaccine component. See the accompanying Focus by Thomas globe4.gif. [CREDIT: C. BICKEL/SCIENCE TRANSLATIONAL MEDICINE]

FRONT PAGE PHOTO CREDIT:
An illustration of the dengue virus, which is transmitted by mosquito bites. (Thomas Splettstoesser/Visuals Unlimited/Corbis) HYPERLINK:http://www.smithsonianmag.com/science-nature/single-protein-root-dengues-virulence-180956544/#2FH2j4Aji6dcqPrb.99 globe4.gif.


Last Modified Date: 09-September-2016



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