BACKGROUND In developed countries, Human Immunodeficiency Virus type-1 (HIV-1) infection has become a chronic disease despite the positive effects of anti-retroviral therapies (ART), but still at least half of the HIV infected population shown signs of cognitive impairment. Therefore, biomarkers of HIV cognitive decline are urgently needed. METHODS We analyze the opening of one of the larger channels expressed by humans, pannexin-1 (Panx-1) channels, in the uninfected and HIV infected population (n = 175). We determined channel opening and secretion of intracellular second messengers released through the channel such as PGE2 and ATP. Also, we correlated the opening of Panx-1 channels with the circulating levels of PGE2 and ATP as well as cogntive status of the individuals analyzed. FINDINGS Here, we demonstrate that Panx-1 channels on fresh PBMCs obtained from uninfected individuals are closed and no significant amounts of PGE2 and ATP are detected in the circulation. In contrast, in all HIV-infected individuals analyzed, even the ones under effective ART, a spontaneous opening of Panx-1 channels and increased circulating levels of PGE2 and ATP were detected. Circulating levels of ATP were correlated with cognitive decline in the HIV-infected population supporting that ATP is a biomarker of cognitive disease in the HIV-infected population. INTERPRETATION We propose that circulating levels of ATP could predict CNS compromise and lead to the breakthroughs necessary to detect and prevent brain compromise in the HIV-infected population.

中文翻译：

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ATP的循环水平是HIV认知障碍的生物标志物。

背景技术在发达国家，尽管抗逆转录病毒疗法（ART）发挥了积极作用，但人类1型免疫缺陷病毒（HIV-1）感染已成为一种慢性疾病，但仍然有至少一半的HIV感染者显示出认知障碍的迹象。 。因此，迫切需要HIV认知能力下降的生物标志物。方法我们分析了在未感染和感染HIV的人群（n = 175）中由人类表达的较大通道之一pannexin-1（Panx-1）的开放性。我们确定了通道的开放和通过通道释放的细胞内第二信使的分泌，例如PGE2和ATP。此外，我们将Panx-1通道的开放与PGE2和ATP的循环水平以及所分析个体的认知状态相关联。结果在这里，我们证明从未感染个体获得的新鲜PBMC上的Panx-1通道是封闭的，并且在循环中未检测到大量PGE2和ATP。相反，在所有接受过HIV感染的个体中，即使是接受有效抗病毒治疗的个体，也都检测到Panx-1通道的自发开放以及PGE2和ATP的循环水平增加。ATP的循环水平与HIV感染人群的认知能力下降相关，这证明ATP是HIV感染人群认知疾病的生物标记。解释我们认为，ATP的循环水平可以预测中枢神经系统的损害，并为检测和预防HIV感染人群的脑损害提供必要的突破。