Natthanej LuplerdlopDorothée MisséDorothy BrayVirginie DeleuzeJean Paul GonzalezVijittra LeardkamolkarnHans YsselFrancisco VeasIRD Centre de MontpellierMahidol UniversityImmunoClin LtdIGMM Institut de Genetique Moleculaire de MontpellierInserm2018-08-202018-08-202006-11-01EMBO Reports. Vol.7, No.11 (2006), 1176-1181146931781469221X2-s2.0-33750499753https://repository.li.mahidol.ac.th/handle/20.500.14594/22955Dengue virus (DV) is an important re-emerging arthropod-borne virus of global significance. The defining characteristic of DV infection-associated pathology is haemorrhagic 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 endothelial 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 endothelial 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 haemorrhagic fever-inducing viruses, and identify a new therapeutic approach for the treatment of viral-induced vascular leakage by specifically targeting gelatinolytic metalloproteases.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/sj.embor.7400814