Thesis Defense Announcement
To: The George Mason University Community
Candidate: Sahar Saleem
Program: M.S. in Biology
Date: Monday July 16, 2018
Time: 2:00 PM
Place: Colgan Hall, Room 204
George Mason University
Science & Tech Campus<http://www.gmu.edu/resources/welcome/Directions-to-GMU.html>
Title: "Characterization of V5 Tagged Rift Valley Fever Virus (RVFV) and Identification of Host Proteins That Interact With RVFV "
Committee Chair: Dr. Kylene Kehn-Hall
Committee Members: Dr. Aarthi Narayanan, Dr. Anne Scherer
This is a public defense and all are invited to attend.
Rift Valley fever virus (RVFV) belongs to the genera Phlebovirus in the family Phenuviridae. It is an arbovirus, which can be transmitted by mosquitoes. RVFV infects livestock and humans. Infection of pregnant ruminants, including goats, sheep and cattle, results in high abortion rates. Rift Valley fever (RVF) ranges from subclinical to fatal and may cause fetal malformation. In adult sheep, the mortality rate is about 20% while lambs have a higher mortality rate. In humans, the incubation period for the virus is about 6-7 days and RVFV presents with a self-limiting febrile illness which includes malaise, headaches and nausea. In some cases the symptoms may progress to neurological disorders, hemorrhagic fever and/or ocular disease. RVFV has been classified as a Category A pathogen by the National Institute of Allergy and Infectious Diseases (NIAID) as it has the potential to cause large outbreaks and poses the highest threat to national security. It is considered an overlap select agent by the Centers of Disease Control (CDC) and United States Department of Agriculture (USDA). There are currently no FDA approved therapies or vaccines available to public for RVFV infection. It therefore is important to look at the interaction of viral proteins with host proteins so they can be targeted for therapeutics against RVFV. Gn is one of the glycoproteins of RVFV which plays an important role in the assembly of the virion. The host protein partners of RVFV Gn are largely unknown. Therefore we aim to identify Gn protein partners using a proteomic (immunoprecipitation followed by mass spectrometry) based approach. To facilitate this analysis and to provide a tool for future research, two V5 tagged MP12 viruses were made namely V5Gn105 and V5Gn229. Our data indicate that the recombinant viruses replicated similar to the parental MP12 virus. Our research identified E3 Ubiquitin-protein ligase UBR4 (UBR4) as one host protein partner that interacts with RVFV Gn. This interaction was confirmed via co-immunoprecipitation analysis. Knockdown of UBR4 decreased RVFV titers by 5-fold and resulted in increased intracellular infectivity. Therefore we hypothesize that UBR4 plays a role in the egress of virions from the cells.