Some of the most deleterious effects associated with dengue-virus infection result from induction of proinflammatory cytokines and overstimulation of the immune system. Cytokines make blood vessels leaky and promote inflammation of tissues, which can lead to internal hemorrhaging and loss of blood fluid from the vasculature, which can result in shock. Macrophages are a major producer of proinflammatory cytokines and a primary target of dengue virus infection.
A C-type lectin domain family 5 (CLEC5A) on the surface of macrophages has now been identified that interacts with an envelope protein on the dengue virus to specifically induce the production of proinflammatory cytokines by macrophages during infection. A collaboration of researchers in Taiwan used a monoclonal antibody to block CLEC5A, and demonstrate that inhibiting this macrophage-virus interaction prevents plasma leakage and hemorrhage in a mouse model. The antibody had an overall pro-survival effect suggesting that this strategy may prove effective for inhibiting severe inflammation and shock associated with certain viral infections.
