Thesis Defense Announcement
To: The George Mason University Community
Candidate: Chelsea Pinkham
Program: M.S. in Biology
Date: Tuesday July 15, 2014
Time: 10:00 a.m.
Place: George Mason University
Prince William Campus<http://www.gmu.edu/resources/welcome/Directions-to-GMU.html>
Bull Run Hall, Room 253
Title: "The Role of Signal Transducer and Activator of Transcription (Stat) Protein in Rift Valley Fever Virus Infection"
Thesis Director: Dr. Kylene Kehn-Hall
Thesis Committee: Dr. Aarthi Narayanan, Dr. Yuntao Wu
A copy of the thesis will be available in the Mercer Library. All are invited to attend the defense.
ABSTRACT
First identified in the Rift Valley of Kenya, Rift Valley Fever Virus (RVFV) is a mosquito-borne zoonotic disease that can cause severe illness in humans and livestock. RVFV outbreaks can have remarkably devastating effects on livestock, in which RVFV causes spontaneous abortion in almost 100% of pregnant ruminants, referred to as an "abortion storm," and a high mortality in young animals. These outbreaks can become a major burden for countries in which RVFV is endemic. Humans can also become infected with RVFV through a bite from an infected mosquito, which in many cases causes an acute febrile illness with symptoms including chills, malaise, dizziness, fever, and headache. In a small percentage of cases, the disease progresses to severe symptoms including blindness, hepatitis, encephalitis, and hemorrhagic fever. With the increased risk of spread, competent species in many areas of the world and the ease of international trade and travel, RVFV is considered an overlap select agent by the Centers of Disease Control and Prevention and the U.S. Department of Agriculture. There are currently no approved vaccines or therapeutics available to the public in order to combat RVFV infection. Current research has focused more on host factors that aid in viral replication, unveiling a new collection of targets for treatments. Signal transducer and activator of transcription (STAT) proteins are a family of transcription factors that regulate many aspects of the host cell, such as immunity, cell growth, survival, and proliferation. The JAK-STAT protein cascade is initiated when a receptor receives signals from external factors, such as cytokines and growth factors, which in turn activate receptor-associated tyrosine kinases. Our research shows that both STAT1 and STAT3 are phosphorylated on their conserved tyrosine residue following RVFV infection. These phosphorylation events are dependent on the viral protein NSs, as the MP12-ÄNSs virus, which has a complete deletion of the viral protein NSs, does not induce STAT1 and STAT3 phosphorylation. Our data also indicates that two specific mutations in NSs impair STAT3 tyrosine phosphorylation. Treatment of cells with a STAT3 small molecular inhibitor, Stattic, reduces MP12 viral titers at 8, 16, and 24 hours post infection. Finally, STAT3 -/- MEFs are more susceptible to RVFV induced cell death than WT MEFs, indicating that STAT3 functions as a pro-survival factor.
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