Dissertation Defense Announcement
To:  The George Mason University Community

Candidate: Forrest Keck
Program: PhD in Biosciences
 
Date:   Wednesday August 1, 2018
Time:   10:00 AM
Place:  George Mason University
 Science & Tech campus
  IABR, Room 1004 
 
Title: "Mitochondrial-Derived Oxidative Stress is a Major Contributor to Venezuelan Equine Encephalitis Virus-Induced Inflammation"

Committee Chair: Dr. Aarthi Narayanan
Committee Members: Dr. Kylene Kehn-Hall, Dr. Anne Verhoeven, Dr. Andrew Cawthon

This is a public defense and all are invited to attend.

ABSTRACT:
Venezuelan equine encephalitis virus (VEEV) is a neurotropic arbovirus that is highly infectious as an aerosol and can result in an encephalitic phenotype in infected individuals. VEEV infections are known to be associated with robust inflammation that eventually contributes to neurodegenerative phenotypes. In this study, we utilize the TC-83 strain of VEEV, which is known to induce the expression of IL-6, IL-8, and other pro-inflammatory cytokines. We had previously demonstrated that TC-83 infection resulted in changes in mitochondrial function, eventually resulting in mitophagy. Our data links upstream mitochondrial dysfunction with downstream inflammation in the context of microglia and astrocytoma cells. We also provide data on the role of bystander cells, which significantly contribute to the overall inflammatory load. Use of a mitochondrial-targeted antioxidant, mitoquinone mesylate, greatly reduced the inflammatory cytokine load and ameliorated bystander cell inflammatory responses more significantly than a broad-spectrum anti-inflammatory compound (BAY 11-7082). Our data suggest that inflammatory mediators, especially IL-1?, may prime naïve cells to infection and lead to increased infection rates in these bystander cells. Cumulatively, our data suggest that the interplay between mitochondrial dysfunction and inflammatory events elicited in a neuronal microenvironment during a TC-83 infection may contribute to the spread of infection.

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