Human Immunodeficiency Virus (HIV-1) has claimed more than 30 million lives. The HIV-1 lifecycle is divided into two alternate states: active replication, characterized by full transcription activity at the viral promoter, or a transcriptionally silent, latent state. Since current therapies only target actively replicating virus, latently infected cells serve as a drug-resistant viral reservoir. HIV-1 utilizes RNA polymerase II pausing to regulate the switch between active replication and latency. The viral TAT protein overcomes pausing by recruiting the cellular kinase P-TEFb to the paused transcription complex. Previously, the Ahlquist lab showed that ZASC1, a cellular transcription factor with strong links to cancer and inherited ataxias, regulates this critical step in the viral lifecycle through sequence-specific DNA-dependent recruitment of TAT and P-TEFb to the viral promoter. Recent work in our group focuses on understanding ZASC1 regulation by signaling pathways and interactions with cellular regulators of transcription. These results will identify new aspects of HIV-1 transcription elongation, potential targets for therapeutic intervention, and have strong implications for the regulation of viral latency as well as the regulation of cellular genes by ZASC1.
Ph.D. Microbiology and Molecular Genetics ,2002, Medical College of Wisconsin
M.S. Applied Molecular Biology, 1996, University of Wisconsin-Parkside
- ZASC1 stimulates HIV-1 transcription elongation by recruiting P-TEFb and TAT to the LTR promoter.
Bruce JW, Reddington R, Mathieu E, Bracken M, Young JA, Ahlquist P.
PLoS Pathog. 2013 Oct;9(10):e1003712. doi: 10.1371/journal.ppat.1003712. Epub 2013 Oct 24.
- ZASC1 knockout mice exhibit an early bone marrow-specific defect in murine leukemia virus replication.
Seidel S, Bruce J, Leblanc M, Lee KF, Fan H, Ahlquist P, Young JA.
Virol J. 2013 Apr 24;10:130. doi: 10.1186/1743-422X-10-130.
- Cellular transcription factor ZASC1 regulates murine leukemia virus transcription.
Bruce JW, Hierl M, Young JA, Ahlquist P.
J Virol. 2010 Aug;84(15):7473-83. doi: 10.1128/JVI.00299-10. Epub 2010 May 19.