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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-BDP-I (J3))
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University of Washington
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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
Bowen, James R; Zimmerman, Matthew G; Suthar, Mehul S (2018) Taking the defensive: Immune control of Zika virus infection. Virus Res 254:21-26
Johnson, Britney; VanBlargan, Laura A; Xu, Wei et al. (2018) Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability. Immunity 48:487-499.e5
Aguilar-Valenzuela, Renan; Netland, Jason; Seo, Young-Jin et al. (2018) Dynamics of Tissue-Specific CD8+ T Cell Responses during West Nile Virus Infection. J Virol 92:
Platt, Derek J; Smith, Amber M; Arora, Nitin et al. (2018) Zika virus-related neurotropic flaviviruses infect human placental explants and cause fetal demise in mice. Sci Transl Med 10:
Chow, Kwan T; Driscoll, Connor; Loo, Yueh-Ming et al. (2018) IRF5 regulates unique subset of genes in dendritic cells during West Nile virus infection. J Leukoc Biol :
Dudley, Dawn M; Van Rompay, Koen K; Coffey, Lark L et al. (2018) Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates. Nat Med 24:1104-1107
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

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