Department of Modeling of Biological Processes, COS Heidelberg / Bioquant, Heidelberg University, Im Neuenheimer Feld 267, Heidelberg 69120, Germany; Colorado State University.
Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Unidad Monterrey, Via del Conocimiento 201, Parque PIIT, Apodaca CP 66600 NL, México.
J Theor Biol. 2019 Jul 21;473:20-27. doi: 10.1016/j.jtbi.2019.04.018. Epub 2019 Apr 17.
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.
即使在联合治疗成功阻止艾滋病进展的情况下,开发这种疾病的治愈方法仍然是一个悬而未决的问题。治愈艾滋病的主要步骤之一是能够消除患者体内潜伏的 HIV 储库。在过去的十年中,多项研究结果表明,病毒蛋白 Tat 在潜伏期的建立中起着主导作用。在这里,我们进行了一项数学研究,以了解 Tat 抑制剂作为病毒抑制剂的潜在作用。为此,我们实现了一个能够再现细胞内动力学的计算模型。通过模拟受 HIV 感染的细胞及其细胞内反馈,我们观察到,通过抑制剂从系统中去除 Tat 蛋白会导致病毒暂时和可逆的抑制。相比之下,我们观察到与 Tat 蛋白相互作用并破坏整合病毒基因组的化合物会产生更持久的病毒抑制。