Horizon 1 1 17 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES Embo Reports 1176-1181 endothelial cells haemorrhagic fever viruses matrix metalloprotease inhibitors plasma leakage SB 3CT 2006 fdi:010037727 ENG Embo Reports 1469-221X CC:0002422795-0022 11 10.1038/sj.embor.7400814 https://www.documentation.ird.fr/hor/fdi:010037727 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2025-01/010037727.pdf 7 Horizon (IRD) 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