Flaviviruses present a major public health problem in the US and worldwide. A role of regulatory T cells (Tregs), potent negative regulators of the adaptive and innate immune responses, in viral infection in general, and in flayivirus infection in particular, is poorly understood. We hypothesize that there are distinct qualitative and quantitative requirements for diverse manifestations of Treg function affecting virus specific responses and associated pathology. These manifestations might vary depending on time during the course of viral infection, localization (secondary lymphoid organs vs. peripheral tissues), and the specific virus type. In this application, we will employ a well-established experimental model of West Nile virus (WNV) infection in mice to investigate a role for Treg cells in flavivirus infection. In our studies, we will test the aforementioned hypotheses by taking advantage of FoxpS8'

Public Health Relevance

Flaviviruses present a major public health threat in the US and worldwide. A role of regulatory T cells, potent negative regulators of the adaptive and innate immune responses, in viral infection in general, and in flavivirus infection in particular, is poorly understood. Our studies will assist in the understanding of immunity to flavivirus infections and help identify therapeutic targets for neuroinvasive viruses that are a significant clinical problem, especially in young, elderly, and immunocompromised patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI083019-05
Application #
8652555
Study Section
Special Emphasis Panel (ZAI1-BDP-I (J3))
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2013
Total Cost
$265,262
Indirect Cost
$64,956
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Pierson, Theodore C; Diamond, Michael S (2018) The emergence of Zika virus and its new clinical syndromes. Nature 560:573-581
Adams Waldorf, Kristina M; Nelson, Branden R; Stencel-Baerenwald, Jennifer E et al. (2018) Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain. Nat Med 24:368-374
Hickman, Heather D; Suthar, Mehul S (2018) Editorial overview: Viral immunology: Generating immunity to diverse viral pathogens. Curr Opin Virol 28:viii-x
Chow, Kwan T; Wilkins, Courtney; Narita, Miwako et al. (2018) Differential and Overlapping Immune Programs Regulated by IRF3 and IRF5 in Plasmacytoid Dendritic Cells. J Immunol 201:3036-3050
Bryan, Marianne A; Giordano, Daniela; Draves, Kevin E et al. (2018) Splenic macrophages are required for protective innate immunity against West Nile virus. PLoS One 13:e0191690
Agner, Shannon C; Klein, Robyn S (2018) Viruses have multiple paths to central nervous system pathology. Curr Opin Neurol 31:313-317
Green, Richard; Ireton, ReneƩ C; Gale Jr, Michael (2018) Interferon-stimulated genes: new platforms and computational approaches. Mamm Genome 29:593-602
Walker, Christie L; Merriam, Audrey A; Ohuma, Eric O et al. (2018) Femur-sparing pattern of abnormal fetal growth in pregnant women from New York City after maternal Zika virus infection. Am J Obstet Gynecol 219:187.e1-187.e20
Hahn, William O; Butler, Noah S; Lindner, Scott E et al. (2018) cGAS-mediated control of blood-stage malaria promotes Plasmodium-specific germinal center responses. JCI Insight 3:
Garber, Charise; Vasek, Michael J; Vollmer, Lauren L et al. (2018) Astrocytes decrease adult neurogenesis during virus-induced memory dysfunction via IL-1. Nat Immunol 19:151-161

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