|Education||BS, University of Texas at Dallas|
Currently, the major barrier to a Human Immunodeficiency Virus (HIV-1) cure is the existence of a latent reservoir of virus in CD4+ T cells. This reservoir arises when HIV-1 infects activated or partially activated CD4+ T cells as they are returning to a quiescent memory state that is non-permissive for viral gene expression. Following cellular activation of the host T cells, these viruses can begin replicating and rekindle the infection. While some integrated proviruses are replication-competent and pose a barrier to an HIV-1 cure, a large proportion is defective. Efforts to eradicate HIV-1 from the latent reservoir have centered on latency reversing agents that induce viral gene expression without global T-cell activation. This “shock and kill” method would induce viral genome expression, and HIV-1 specific CD8+ T cells would then kill infected cells. In order to successfully evaluate latency reversing therapy, it is necessary to accurately measure the latent reservoir. Currently, there are no accurate methods to measure and distinguish proviruses with intact genomes from defective proviruses. For my thesis project, I am characterizing the types of proviruses found in patients treated either early or late in the course of HIV-1 infection as well as developing a rapid and scalable assay for the HIV-1 latent reservoir that can distinguish intact from defective genomes.
- Bruner KM, Murray AJ, Pollack RA, Soliman MG, Laskey SB, Capoferri AA, Lai J, Strain MC, Lada SM, Hoh R, Ho YC, Richman DD, Deeks SG, Siliciano JD, Siliciano RF. Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat Med. 2016 Aug 8. [Epub ahead of print] PMID:27500724
- Laskey SB, Pohlmeyer CW, Bruner KM, Siliciano RF. Evaluating Clonal Expansion of HIV-Infected Cells: Optimization of PCR Strategies to Predict Clonality. PLoS Pathog. 2016 Aug 5;12(8):e1005689. eCollection 2016 Aug. PMID:27494508
- Bruner KM, Hosmane NN, Siliciano RF. Towards an HIV-1 cure: measuring the latent reservoir. Trends Microbiol. 2015 Apr;23(4):192-203Epub 2015 Mar 5. Review. PMID:25747663