Ajasin David, Eugenin Eliseo A
Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch, Galveston, TX, United States.
Front Cell Infect Microbiol. 2020 Feb 25;10:61. doi: 10.3389/fcimb.2020.00061. eCollection 2020.
HIV Tat protein is a critical protein that plays multiple roles in HIV pathogenesis. While its role as the transactivator of HIV transcription is well-established, other non-viral replication-associated functions have been described in several HIV-comorbidities even in the current antiretroviral therapy (ART) era. HIV Tat protein is produced and released into the extracellular space from cells with active HIV replication or from latently HIV-infected cells into neighboring uninfected cells even in the absence of active HIV replication and viral production due to effective ART. Neighboring uninfected and HIV-infected cells can take up the released Tat resulting in the upregulation of inflammatory genes and activation of pathways that leads to cytotoxicity observed in several comorbidities such as HIV associated neurocognitive disorder (HAND), HIV associated cardiovascular impairment, and accelerated aging. Thus, understanding how Tat modulates host and viral response is important in designing novel therapeutic approaches to target the chronic inflammatory effects of soluble viral proteins in HIV infection.
HIV反式激活转录蛋白（HIV Tat蛋白）是一种关键蛋白，在HIV发病机制中发挥多种作用。虽然其作为HIV转录反式激活因子的作用已得到充分证实，但即使在当前抗逆转录病毒疗法（ART）时代，在几种HIV合并症中也已描述了其他与病毒复制无关的功能。HIV Tat蛋白由具有活跃HIV复制的细胞产生并释放到细胞外空间，或者从潜伏感染HIV的细胞释放到邻近未感染细胞中，即使在有效的ART导致无活跃HIV复制和病毒产生的情况下也是如此。邻近的未感染细胞和感染HIV的细胞可以摄取释放的Tat，导致炎症基因上调和通路激活，从而在几种合并症中观察到细胞毒性，如HIV相关神经认知障碍（HAND）、HIV相关心血管损伤和加速衰老。因此，了解Tat如何调节宿主和病毒反应对于设计新的治疗方法以靶向HIV感染中可溶性病毒蛋白的慢性炎症效应至关重要。
