Modeling the effect of tat inhibitors on HIV latency

• Published in: Journal of theoretical biology 2019-07, Vol.473, p.20-27
• Main Authors: Aguilera, Luis U., Rodríguez-González, Jesús
• Format: Article
• Language: English
• Subjects: Stochastic model; Tat circuit; Viral suppression
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2019.04.018

•Mathematical study to understand Tat-inhibitors as virus-suppressing agents.•HIV-productive and latent cell phenotypes are described by stochastictransitions.•Competitive and non-competitive inhibitors produce reversible viral suppression.•Didehydro-Cortistatin A (dCA) achieves a more permanent viral inhibition. [Display omitted] Even in the presence of a successful combination therapy stalling the progress of AIDS, developing a cure for this disease is still an open question. One of the major steps towards a cure would be to be able to eradicate latent HIV reservoirs present in patients. During the last decade, multiple findings point to the dominant role of the viral protein Tat in the establishment of latency. Here we present a mathematical study to understand the potential role of Tat inhibitors as virus-suppressing agents. For this aim, we implemented a computational model that reproduces intracellular dynamics. Simulating an HIV-infected cell and its intracellular feedback we observed that removing Tat protein from the system via inhibitors resulted in a temporary and reversible viral suppression. In contrast, we observed that compounds that interact with Tat protein and disrupt the integrated viral genome produced a more permanent viral suppression.