Thesis Defense Announcement
To:  The George Mason University Community

Candidate: Taylor Goad

Program: M.S. in Biology



Date:   Wednesday April 22, 2015

Time:   10:30 AM

Place:  George Mason University
             Prince<http://www.gmu.edu/resources/welcome/Directions-to-GMU.html> William Campus
             Bull Run Hall, Room 249



Title: "Identification of a CBF--RUNX1 Inhibitor that Blocks HIV-1 Infection"
Thesis Director: Dr. Yuntao Wu
Thesis Committee:  Dr. Kylene Kehn-Hall, Dr. Jia Guo
A copy of the thesis will be available in the Mercer Library.  All are invited to attend the defense.
ABSTRACT
Human Immunodeficiency Virus (HIV) is a single-stranded RNA retrovirus and the causative agent of Acquired Immunodeficiency Syndrome (AIDS).  Established antiretroviral therapy (ART) is mostly efficient in reducing viral load in patients, yet several circumstances may necessitate switching patients to new combination therapies.  Drug incompatibility, serious side effects, and the emergence of drug resistance all illustrate the need for a wide selection of antivirals which can be used as second line drugs.  We have performed an anti-HIV drug screening using an HIV-1 Rev-dependent indicator cell line, Rev-CEM-GFP-Luc. Our screening led to the identification of a small molecule inhibitor that has been previously shown to block the association of two cellular transcription factors, CBF- (core-binding factor subunit beta) and RUNX1. We demonstrate that this inhibitor blocks HIV infection by inhibiting viral transcription.  Previous studies have also suggested that the viral protein Vif interacts with CBF-, facilitating polyubiquitination and the degradation of the host restriction factor, APOBEC3G (A3G).  Additionally, the Vif-CBF- binding interface may partially overlap with that of the CBF- binding partner, RUNX1. Given that the identified drug is known to inhibit CBF- - RUNX1 association, we are exploring the possibility that this drug may also interfere with Vif-CBF- interaction, facilitating the incorporation of A3G into budding viruses.
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