Dengue-virus-infected dendritic cells trigger vascular leakage through metalloproteinase overproduction.

نویسندگان

  • Natthanej Luplertlop
  • Dorothée Missé
  • Dorothy Bray
  • Virginie Deleuze
  • Jean-Paul Gonzalez
  • Vijittra Leardkamolkarn
  • Hans Yssel
  • Francisco Veas
چکیده

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.

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عنوان ژورنال:
  • EMBO reports

دوره 7 11  شماره 

صفحات  -

تاریخ انتشار 2006