Identification of a CBF-β RUNX1 Inhibitor Which Blocks HIV-1 Infection
Date
2015-10-23
Authors
Goad, Taylor
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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. After a preliminary anti-HIV drug screening, our lab has identified of a small molecule inhibitor of HIV-1 replication. This drug has been reported to block the association of two cellular transcription factors, CBF-β (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-β, facilitating polyubiquitination and the degradation of the host restriction factor, APOBEC3G (A3G). Furthermore, the Vif-CBF-β binding interface may partially overlap with that of the CBF-β binding partner, RUNX1. Given that the identified drug is known to inhibit CBF-β - RUNX1 association, we are exploring the possibility that this drug may also interfere with Vif-CBF-β interaction, facilitating the incorporation of A3G into budding viruses.
Description
This work was embargoed by the author and will not be publicly available until May 2016.
Keywords
HIV, Antiretroviral therapy, RUNX, APOBEC3G, CBF-β, Inhibitor