Cardif-Mediated Signaling Controls the Initial Innate Response to Dengue Virus In Vivo

The role of Cardif-dependent signaling in controlling dengue virus (DENV) infection and regulating type I interferon (IFN) production in vivo was examined in Cardif-deficient mice. DENV RNA levels were significantly elevated in both the serum and lymphoid tissues of Cardif/ mice at early times compared to those in wild-type animals. Type I IFN production was delayed in these locales of Cardif/ mice until 18 h postin-fection, indicating that Cardif regulates the initial type I IFN response in lymphoid tissues. In contrast, DENV viral loads in nonlymphoid tissues were similar between Cardif/ and wild-type mice. These results reveal that RNA helicase-mediated sensing acts as a first line of innate defense against DENV infection in vivo and functions in a tissue-dependent manner. Dengue virus (DENV) is a positive-sense, single-stranded RNA virus that belongs to the family Flaviviridae, which in-cludes other arthropod-borne viruses such as Japanese enceph-alitis, yellow fever, and West Nile viruses (12). DENV is trans-mitted to humans by mosquitoes and causes an estimated 50 million new cases of dengue fever and 250,000 cases of dengue hemorrhagic fever/dengue shock syndrome per year worldwid