Ebola virus is a category A priority pathogen and a causative agent of viral hemorrhagic fever. Enhanced pathogenicity displayed by the Ebola virus is achieved through simultaneous inhibition of host immune responses and enhanced production of viral proteins and RNA. However, the exact nature of the interactions between the Ebola virus and host cells that promote viral infection and propagation are poorly understood. Consequently, no vaccines or antiviral agents against Ebola are currently available. These factors combined, underscore the need for detailed structural and functional characterization of the Ebola viral components. Ebola VP35 protein is an important virulence factor required in several viral lifecycle stages, including viral assembly, genome replication, packaging, viral transcription, and antiviral activity toward the host innate immune system. Overall goal of the research program is to explore host-viral interactions that lead to immune evasion. The proposed study, using recombinantly expressed non-infectious VP35 protein, will examine the structure of VP35 and characterize its antiviral activity using biochemical methods. These studies will significantly improve our understanding of how VP35 functions to enhance viral pathogenesis and facilitate the design of novel diagnostic and therapeutic strategies to disrupt critical host-pathogen interactions.

Public Health Relevance

Growing concerns of rare but increasing Ebola outbreaks among human populations, coupled with a rising potential of misuse in the form of bioterrorism, underscore the importance of developing a greater understanding of viral components that make Ebola virus a significant threat to global human health. Ebola VP35 is responsible for immune suppression and it can enhance viral replication. Work described in this proposal will characterize the structure and mechanistic basis for innate immune antagonism by Ebola viral VP35 protein, which will provide potential targets to therapeutic interventions and design of cell biological reagents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI081914-05
Application #
8286369
Study Section
Virology - A Study Section (VIRA)
Program Officer
Repik, Patricia M
Project Start
2009-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2012
Total Cost
$372,438
Indirect Cost
$127,413
Name
Washington University
Department
Pathology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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