Thesis Defense Announcement
To:  The George Mason University Community

Candidate: Kelsey Voss
Program: M.S. in Biology
Date:   Wednesday July 9, 2014
Time:   10:00 a.m.
Place:  George Mason University
             Prince William Campus
             Bull Run Hall, Room 253
Title: "Role of Extracellular Signal-Regulated Kinase (ERK) in New World Alphavirus Multiplication"

Thesis Director: Dr. Aarthi Narayanan

Thesis Committee:  Dr. Kylene Kehn-Hall, Dr. Monique van Hoek
A copy of the thesis will be available in the Mercer Library.  All are invited to attend the defense.

New World alphaviruses belonging to the family Togaviridae are known to infect humans and equines and cause encephalitic disease. The New World alphaviruses are classified as emerging infectious agents and Category B select agent pathogens. There are concentrated efforts dedicated to the development of medical countermeasures to New World alphavirus infections including therapeutics and vaccines. Our current study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. We demonstrate that infection of human astrocytoma cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of many signaling nodes of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Time of addition studies reveal that Ag-126-mediated inhibition of VEEV occurred during the early stages of the infectious process. While our studies revealed that expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear and cytoplasmic distribution of the viral capsid protein. Studies focused on the survival of host cells in the presence of Ag-126 indicated an increased percentage of cells that survive the infection in the presence of Ag-126. Finally, extending our studies to virulent strains of VEEV, Eastern and Western equine encephalitis viruses (EEEV and WEEV) revealed that Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses