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Article Dans Une Revue EMBO Reports Année : 2006

Dengue‐virus‐infected dendritic cells trigger vascular leakage through metalloproteinase overproduction

Résumé

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.

Dates et versions

hal-02960085 , version 1 (07-10-2020)

Identifiants

Citer

Natthanej Luplerdlop, Dorothée Missé, Dorothy Bray, Virginie Deleuze, Jean-Paul Gonzalez, et al.. Dengue‐virus‐infected dendritic cells trigger vascular leakage through metalloproteinase overproduction. EMBO Reports, 2006, 7 (11), pp.1176-1181. ⟨10.1038/sj.embor.7400814⟩. ⟨hal-02960085⟩
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