Viral infection triggers the production of interferons; however, dengue virus can suppress this antiviral response. In the Journal of Virology, He et al. show that the dengue virus non-structural protein NS4a subverts induction of the production of type I interferons by interfering with the RIG-I–MAVS activation pathway. The recognition of viral RNA by the RNA helicase RIG-I triggers interactions between the caspase-recruitment domains of RIG-I and those of the signaling adaptor MAVS that lead to activation of kinase TBK1 and the expression of genes encoding antiviral products, including Ifnb, mediated by the transcription factor IRF3. NS4a potently disrupts this interaction by binding to the MAVS caspase-recruitment and carboxyl-terminal domains and thereby prevents Ifnb expression. NS4a localizes to the mitochondrial membrane, and the transmembrane domain 3 can mediate inhibition of MAVS. These findings suggest targeting NS4a or its ability to interact with MAVS might enhance innate antiviral responses to dengue.

J. Virol. (1 Jun 2016) doi:10.1128/JVI.00221-16