Flavivirus NS1 Triggers Tissue-Specific Vascular Endothelial Dysfunction Reflecting Disease Tropism.

Authors:
Dustin R Glasner
Dustin R Glasner
Laboratory of Retroviruses
Diego A Espinosa
Diego A Espinosa
Johns Hopkins Bloomberg School of Public Health
United States
Scott B Biering
Scott B Biering
University of Chicago
Kalani Ratnasiri
Kalani Ratnasiri
School of Public Health
Ann Arbor | United States
Chunling Wang
Chunling Wang
Tianjin University of Science and Technology
China

Cell Rep 2019 Feb;26(6):1598-1613.e8

Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. Electronic address:

Flaviviruses cause systemic or neurotropic-encephalitic pathology in humans. The flavivirus nonstructural protein 1 (NS1) is a secreted glycoprotein involved in viral replication, immune evasion, and vascular leakage during dengue virus infection. However, the contribution of secreted NS1 from related flaviviruses to viral pathogenesis remains unknown. Here, we demonstrate that NS1 from dengue, Zika, West Nile, Japanese encephalitis, and yellow fever viruses selectively binds to and alters permeability of human endothelial cells from lung, dermis, umbilical vein, brain, and liver in vitro and causes tissue-specific vascular leakage in mice, reflecting the pathophysiology of each flavivirus. Mechanistically, each flavivirus NS1 leads to differential disruption of endothelial glycocalyx components, resulting in endothelial hyperpermeability. Our findings reveal the capacity of a secreted viral protein to modulate endothelial barrier function in a tissue-specific manner both in vitro and in vivo, potentially influencing virus dissemination and pathogenesis and providing targets for antiviral therapies and vaccine development.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2019.01.036DOI Listing
February 2019
6 Reads

Publication Analysis

Top Keywords

vascular leakage
8
flavivirus ns1
8
tissue-specific vascular
8
endothelial
5
yellow fever
4
endothelial barrier
4
encephalitis yellow
4
alters permeability
4
japanese encephalitis
4
barrier function
4
fever viruses
4
flavivirus
4
selectively binds
4
modulate endothelial
4
protein modulate
4
function tissue-specific
4
viruses selectively
4
binds alters
4
tissue-specific manner
4
in vitro in vivo
4

Altmetric Statistics

Similar Publications