Grant: $394,000 - National Institutes of Health - Aug. 11, 2009
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Award Description: West Nile virus (WNV) is an NIAID Category B infectious agent that can cause severe encephalitis, encephalopathym and paralysis in humans and other animals. Pathogenic WNV has emerged into the Western hemisphere and presents a serious public health threat. Elucidating processes that support WNV infection, cell tropism, and virus spread will provide insights for novel stategies for intervention. The virus-host interactions that control WNV infection are not well-defined. Our preliminary studies have revealed that the cell tropism of WNV infection, and infection outcome, are in part controlled by the host innate antiviral response and the actions of type 1 interferon (IFN) that are induced during infection. We have found that WNV triggers the innate antiviral response within infected tissues and cells, and that this response and IFN actions restrict cell tropism of infection. Our studies show that WNV can also disrupt IFN signaling and attenuate the innate antiviral response, and that the ability to alter the host IFN response contributes to neurovirulence and pathogenesis among strains. These observations define the innate host response and virus countermeasures of IFN action as key determinants controlling immunity and pathogenesis of WNV infection. We hypothesize that differential triggering and control of the host response and IFN effector actions among cell types/tissues and by WNV strains defines cell tropism, virulence, and infection outcome. Our studies will define the virus/host interface of WNV infection, and provide novel insights to guide therapeutic and vaccine strategies aimed at modulating immunity to infection.
Project Description: The award for this project was just received approxiamtely 2 weeks ago. We have now initiated our Aim 1 studies to define the pathogen recognition receptor signaling pathways that mediate the innate immune reponse to West Nile virus in specific cell types. The research activities at the University of Washington on this project currently include conducting in vitro studies of cell signaling for pathway analyses. In addition, Dr. Michael Diamond (Washington University) is a subcontractor on this project. His group is currently engaged in assessing the role of the IRF-3 signaling pathway in West Nile virus infection and innate immunity.
Jobs Summary: ASSOCIATE PROFESSOR-Requires a record of substantial success in both teaching and research, except that in unusual cases an outstanding record in one of these activities may be considered sufficient. PREDOCTORAL RESEARCH ASSOCIATE 2-Engage in research on sponsored projects under general supv of faculty/research staff. May include independent research under the guidance of a faculty member. Normally a doctoral candidate. RESEARCH SCIENTIST/ENGINEER - ASSISTANT-Entry level position, performing assigned tasks under immediate supervision, applying standard scientific procedures and techniques based on pre-established guidelines or instructions. RESEARCH SCIENTIST/ENGINEER 1-Perform routine science or engineering work, responsible for evaluating, selecting and applying scientific techniques or procedures to assignments with clear and specific objectives. RESEARCH SCIENTIST/ENGINEER 3-Independently select and apply techniques or procedures to assignments of moderate complexity, potentially involving conflicting design requirements, unavailability of materials or resources. SENIOR FELLOW-Works under the direction of PI for the benefit of the research programs, the department's educational program, and their own professional growth. In most most fields marked by a doctoral degree. (Total jobs reported: 0)
Project Status: Less Than 50% Completed
This award's data was last updated on Aug. 11, 2009. Help expand these official descriptions using the wiki below.