%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Luplerdlop, Natthanej
%A Missé, Dorothée
%A Bray, D.
%A Deleuze, V.
%A Gonzalez, Jean-Paul
%A Leardkamolkarn, V.
%A Yssel, H.
%A Veas, Francisco
%T Dengue-virus-infected dendritic cells trigger vascular leakage through metalloproteinase overproduction
%D 2006
%L fdi:010037727
%G ENG
%J Embo Reports
%@ 1469-221X
%K endothelial cells ; haemorrhagic fever viruses ; matrix metalloprotease inhibitors ; plasma leakage ; SB 3CT
%M CC:0002422795-0022
%N 11
%P 1176-1181
%R 10.1038/sj.embor.7400814
%U https://www.documentation.ird.fr/hor/fdi:010037727
%> https://www.documentation.ird.fr/intranet/publi/2007/01/010037727.pdf
%V 7
%W Horizon (IRD)
%X Dengue virus (DV) is an important re-emerging arthropod-borne virus of global significance. The defining characteristic of DV infection-associated pathology is haernorrhagic fever, which often leads to a fatal shock-like syndrome (DHF/DSS) owing to an increase in vascular endothelial permeability. Here, we show, in a viral dose-dependent manner, that DV-infected immature dendritic cells overproduce soluble gelatinolytic matrix metalloproteinase (MMP)-9-and to a lesser extent MMP-2-which enhances enclothelial permeability, but which are reduced by specific inhibitors and a neutralizing anti-MMP-9 antibody. This permeability was associated with a loss of expression of the platelet enclothelial adhesion molecule 1 (PECAM-1) and vascular endothelium (VE)-cadherin cell adhesion molecules and redistribution of F-actin fibres. These in vitro observations were confirmed in an in vivo vascular-leakage mouse model. These results provide a molecular basis for DHF/DSS that could be a basis for a general model of haernorrhagic fever-inducing viruses, and identify a new therapeutic approach for the treatment of viral-induced vascular leakage by specifically targeting gelatinolytic metal loproteases.
%$ 052