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 postinfection, 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.
Perry
Stuart T
ST
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Prestwood
Tyler R
TR
Lada
Steven M
SM
Benedict
Chris A
CA
Shresta
Sujan
S
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D007370:Interferon Type I; C512612:MAVS protein, mouse