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New Defense Mechanism Against Dengue Identified in Mosquitoes

Dengue fever is caused by any of four serotypes of dengue virus, all of which are transmitted by mosquitoes. Interestingly, mosquitoes have an innate immune system capable of effectively defending against a number of viruses, including dengue.

Mosquito immune responses are largely coordinated by three signaling pathways: the Toll, the Immune Deficiency (IMD), and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. Previous studies have shown that the well-characterized Toll and IMD pathways are involved in the mosquito’s anti-dengue response. However, until now, relatively little has been known about the role of the JAK-STAT pathway.

NIAID-supported researchers at Johns Hopkins University have been examining the immune system of Aedes aegypti, the primary mosquito vector of dengue, to determine what, if any, part the JAK-STAT pathway plays in regulating dengue infection. Led by Dr. George Dimopolous, the team discovered that dengue virus infection in A. aegypti mosquitoes does, in fact, activate the JAK-STAT immune signaling pathway. Researchers learned that the mosquito’s susceptibility to dengue virus infection increases when the JAK-STAT pathway is suppressed and that mosquitoes become more resistant to the virus when the negative regulator of the JAK-STAT pathway, the PIAS protein, is silenced.

These results show that the JAK-STAT pathway is an important component of the mosquito immune system’s fight against dengue viruses and suggest that this pathway may act independently of the Toll and IMD pathways. Such knowledge is important because it identifies an additional route to block transmission of this dengue to humans.

Souza-Neto J et al. An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Published online before print October 1, 2009, doi: 10.1073/pnas.0905006106.

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Last Updated November 10, 2009