Abstract

West Nile virus (WNV) is an emerging infectious disease of public health importance. In humans, WNV can cause a life threatening illness and damage to the central nervous system (CNS). We have linked WNV infection outcome with the regulation of host cell pathogen recognition receptor (PRR) signaling programs of innate immunity that trigger interferon alpha/beta expression and that activate interferon regulatory factors (IRFs) to induce antiviral response genes that control infection. We now propose to determine the specific PRRs, IRFs, and their intracellular signaling pathways that control cell-specific imimune defenses and the outcome of WNV infection. Our studies will 1) Determine the effect of specific PRR and IRF genes on cell tropism of WNV infection, and 2) Define the PRRs and IRFs that serve to control CNS entry and pathogenesis of WNV infection. These studies will reveal the host innate immune signaling and response features that control WNV infection.

Public Health Relevance

West Nile virus (WNV) is an emerging infectious disease of public health importance. In humans, WNV can cause a life threatening illness and damage to the central nervous system. We have linked WNV infection outcome with viral measures to trigger and control innate immunity. Our studies will define the innate immune functions that control WNV infection and spread.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI074973-02
Application #
7914331
Study Section
Immunity and Host Defense Study Section (IHD)
Program Officer
Repik, Patricia M
Project Start
2009-08-14
Project End
2011-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
2
Fiscal Year
2010
Total Cost
$380,000
Indirect Cost

  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

Luo, Huanle; Winkelmann, Evandro; Xie, Guorui et al. (2017) MAVS Is Essential for Primary CD4+ T Cell Immunity but Not for Recall T Cell Responses following an Attenuated West Nile Virus Infection. J Virol 91:
Quicke, Kendra M; Diamond, Michael S; Suthar, Mehul S (2017) Negative regulators of the RIG-I-like receptor signaling pathway. Eur J Immunol 47:615-628
Zhao, Jincun; Vijay, Rahul; Zhao, Jingxian et al. (2016) MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis. J Virol 90:7098-7108
Nair, Sharmila; Diamond, Michael S (2015) Innate immune interactions within the central nervous system modulate pathogenesis of viral infections. Curr Opin Immunol 36:47-53
Lazear, Helen M; Nice, Timothy J; Diamond, Michael S (2015) Interferon-?: Immune Functions at Barrier Surfaces and Beyond. Immunity 43:15-28
Lazear, Helen M; Daniels, Brian P; Pinto, Amelia K et al. (2015) Interferon-? restricts West Nile virus neuroinvasion by tightening the blood-brain barrier. Sci Transl Med 7:284ra59
Kell, Alison M; Gale Jr, Michael (2015) RIG-I in RNA virus recognition. Virology 479-480:110-21
Chakrabarti, Arindam; Banerjee, Shuvojit; Franchi, Luigi et al. (2015) RNase L activates the NLRP3 inflammasome during viral infections. Cell Host Microbe 17:466-77
Hussmann, Katherine L; Vandergaast, Rianna; Ochsner, Susan Park et al. (2014) In vitro and in vivo characterization of a West Nile virus MAD78 infectious clone. Arch Virol 159:3113-8
Zhao, Jincun; Li, Kun; Wohlford-Lenane, Christine et al. (2014) Rapid generation of a mouse model for Middle East respiratory syndrome. Proc Natl Acad Sci U S A 111:4970-5

Showing the most recent 10 out of 28 publications