Journal of virology 2016 12 14() pii JVI.01606-16
Dengue virus (DENV) is a member of the Flavivirus genus of viruses and can result in severe febrile illness. Here we show that FLJ11286, which we refer to as IRAV, is induced by DENV in an interferon-dependent manner, displays antiviral activity against DENV, and localizes to the DENV replication complex. IRAV is an RNA binding protein and localizes to cytoplasmic processing bodies (P-bodies) in uninfected cells, where it interacts with the MOV10 RISC complex RNA helicase, suggesting a role for IRAV in the processing of viral RNA. After DENV infection, IRAV, along with MOV10 and Xrn1, localize to the DENV replication complex and associate with DENV proteins. Depletion of IRAV or MOV10, results in an increase in viral RNA. These data serve to characterize an interferon-stimulated gene with antiviral activity against DENV as well as to propose a mechanism of activity involving the processing of viral RNA.
Dengue virus, a member of the Flaviviridae family of viruses, can result in a life threatening illness and has significant impact on global health. Dengue has been shown to be particularly sensitive to the effects of type-I interferon, however, little is known about the mechanisms by which interferon-stimulated genes function to inhibit viral replication. A better understanding of the interferon-mediated antiviral response to dengue may aid in development of novel therapeutics. Here, we examine the influence of the interferon-stimulated gene IRAV (FLJ11286) on dengue virus replication. We show that IRAV associates with P-bodies in uninfected cells and with the dengue replication complex after infection. IRAV also interacts with MOV10, depletion of which is associated with increased viral replication. Our results provide insight into a newly identified antiviral gene as well as well as broaden our understanding of the innate immune response to dengue virus infection.