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Journal of Virology, August 2009, p. 8276-8281, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00365-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Stuart T. Perry,1 Tyler R. Prestwood,1 Steven M. Lada,1 Chris A. Benedict,2 and Sujan Shresta1*

Division of Vaccine Discovery,1 Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 920372

Received 18 February 2009/ Accepted 26 May 2009

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.

* Corresponding author. Mailing address: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037. Phone: (858) 752-6944. Fax: (858) 752-6987. E-mail: sujan{at}liai.org

{triangledown} Published ahead of print on 3 June 2009.

Journal of Virology, August 2009, p. 8276-8281, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00365-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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