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First Potential Treatment for Dengue

Millions of people are affected by dengue globally. Dengue is a viral disease transmitted by mosquitoes of the genus Aedes. Dengue shock syndrome is a fatal shock associated// with severe blood loss, though there may or may not be any hemorrhage. The pathology of this disease is unknown thus there is no treatment or vaccine available. The only prevention 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 of the infected cells, consequently containing the metalloproteinases, were brought into contact with this tissue. The vascular p
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