Abstract

This proposed research seeks to understand how virus and host control innate immune defenses and the outcome of WNV infection. WNV is described as a model flavivirus which is representative of other members of the family. The PL has defined specific PRR pathways and IRFs as key to immune triggering and programming during WNV infection. It is hypothesized that viral triggering and control of PRR and signaling programs and innate immune defenses of the host cell defines the tissue tropism and virulence properties of WNV infection. The PL proposes to conduct in vitro and in vivo studies to 1) define cell specific PRR pathways that trigger innate immunity against WNV 2) Identify the IFN stimulated innate immune effector genes that control WNV replication and 3) determine the molecular mechanism by which pathogenic WNV evades the innate immune actions of IFN?/?.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI083019-04
Application #
8261950
Study Section
Special Emphasis Panel (ZAI1-BDP-I (J3))
Program Officer
Miller, Lara R
Project Start
2009-05-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
4
Fiscal Year
2012
Total Cost
$2,065,365
Indirect Cost
$458,660

  Institution

Name
University of Washington
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

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
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, Reneé 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:

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