Dengue and other hemorrhagic fevers: Towards a first potential treatment

Globally, 60 to 100 million people are hit by Dengue, a viral disease transmitted by mosquitoes of the genus Aedes. The most severe form of this disease, which causes blood loss, can lead to a fatal shock-like state (Dengue Shock Syndrome) with or without associated haemorrhage, and is currently increasing in tropical countries. The pathological mechanisms of Dengue are still unknown and it has not been possible to produce any treatment or vaccine. The only current prevention method is vector control.

This context brought IRD immunology and virology specialists and their research partners (1) to focus on these little-known biological mechanisms that are set into operation on infection by the virus, responsible for increasing the permeability of vascular wall endothelial cells and hence blood loss. The researchers found evidence of the role played by particular enzymes, metalloproteinases, in the occurrence of this leakage.

Low concentrations of these enzymes are present naturally in the organism, and they are involved in the reconfiguration of organ tissues during human embryonic development or tissue repair, but also in the development of certain cancers. They attack specifically the intercellular cement that binds the vascular walls. The research team demonstrated, in vitro, that Dengue-virus infection of certain targeted cells of the immune system (the dendritic cells) triggered an inflammatory reaction, stimulating these same target cells to overproduce metalloproteinases (gelatinolytic matrix metalloproteinases MMP-9) and secrete them into the cellular supernatant (2). The quantity of enzyme produced therefore appears to be proportional to the concentration of viral particles present.

To verify that the metalloproteinases were the only agents responsible for the increased vascular permeability, the researchers performed tests on cell cultures of endothelial tissue, of the same type as that of the blood vessel walls. The supernatant

Contact: Guillaume-Signoret Marie
Institut de Recherche Pour le Dveloppement

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