Presentation Time: 2:45-3:05
Home University: UNC-Chapel Hill
Research Mentor: Guochun Jiang, Global Health and Infectious Disease
Program: SMART
Research Title: Kynurenine metabolism induces HIV latency disruption and induces ACSS2-associated histone crotonylation
The Human Immunodeficiency Virus-1 (HIV) and the Acquired Immunodeficiency syndrome (AIDS) it causes remain incurable. Much has been done to reduce the effects and transmissibility of the disease, with antiretroviral therapy (ART) being a prime example. However, it is necessary to establish a method to completely rid the body of latent and residual active HIV. With a “shock and kill” strategy, latent HIV could be disrupted to express viral proteins and be subsequently targeted for clearance by alternate treatments. A previous study suggests that the tryptophan metabolic pathway may offer insight into potential latency reversal mechanisms, where the tryptophan metabolite, kynurenine, was tested in various modified HIV-latent cell lines to disrupt HIV latency. We hypothesize that the regulation of HIV transcription by tryptophan metabolism may be via epigenetic modification of histone tails at HIV LTR. Treatment is administered for 24-72 hours and cells are harvested for flow cytometry and protein extractions. Preliminary results demonstrate that supplement of kynurenine induces has some effect in the expression of HIV gene transcription in both of the HIV latency models. Results of these experiments further elucidate that kynurenine enhances the levels of ACSS2 and AhR, which may induce histone crotonylation. The potential chemical properties and pathways the treatments interact with could be established as an effective strategy to tackle HIV infection and aid in its potential purge from patients.