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Dengue‐virus‐infected dendritic cells trigger vascular leakage through metalloproteinase overproduction
Author(s) -
Luplertlop Natthanej,
Missé Dorothée,
Bray Dorothy,
Deleuze Virginie,
Gonzalez JeanPaul,
Leardkamolkarn Vijittra,
Yssel Hans,
Veas Francisco
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400868
Subject(s) - dengue virus , dengue fever , vascular permeability , virus , matrix metalloproteinase , metalloproteinase , virology , biology , endothelial stem cell , endothelium , in vivo , in vitro , cell adhesion molecule , immunology , microbiology and biotechnology , biochemistry , endocrinology
Dengue 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.