Malik Shaily, Eugenin Eliseo A
Public Health Research Institute (PHRI) and Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
Curr HIV Res. 2016;14(5):400-411. doi: 10.2174/1570162x14666160324124558.
One of the major complications of Human Immunodeficiency Virus (HIV) infection is the development of HIV-Associated Neurocognitive Disorders (HANDs) in approximately 50-60% of HIV infected individuals. Despite undetectable viral loads in the periphery owing to anti-retroviral therapy, neuroinflammation and neurocognitive impairment are still prevalent in HIV infected individuals. Several studies indicate that the central nervous system (CNS) abnormalities observed in HIV infected individuals are not a direct effect of viral replication in the CNS, rather these neurological abnormalities are associated with amplification of HIV specific signals by unknown mechanisms. We propose that some of these mechanisms of damage amplification are mediated by gap junction channels, pannexin and connexin hemichannels, tunneling nanotubes and microvesicles/exosomes.
Our laboratory and others have demonstrated that HIV infection targets cell to cell communication by altering all these communication systems resulting in enhanced bystander apoptosis of uninfected cells, inflammation and viral infection. Here we discuss the role of these communication systems in HIV neuropathogenesis.
In the current manuscript, we have described the mechanisms by which HIV "hijacks" these host cellular communication systems, leading to exacerbation of HIV neuropathogenesis, and to simultaneously promote the survival of HIV infected cells, resulting in the establishment of viral reservoirs.
人类免疫缺陷病毒（HIV）感染的主要并发症之一是约50%-60%的HIV感染者会出现HIV相关神经认知障碍（HANDs）。尽管抗逆转录病毒疗法使外周血中的病毒载量检测不到，但神经炎症和神经认知障碍在HIV感染者中仍然普遍存在。多项研究表明，在HIV感染者中观察到的中枢神经系统（CNS）异常并非CNS中病毒复制的直接结果，而是这些神经学异常与通过未知机制放大HIV特异性信号有关。我们提出，这些损伤放大机制中的一些是由缝隙连接通道、泛连接蛋白和连接蛋白半通道、隧道纳米管以及微泡/外泌体介导的。
我们实验室及其他研究已证明，HIV感染通过改变所有这些通讯系统来靶向细胞间通讯，从而导致未感染细胞的旁观者凋亡增加、炎症反应和病毒感染。在此，我们讨论这些通讯系统在HIV神经发病机制中的作用。
在当前的手稿中，我们描述了HIV“劫持”这些宿主细胞通讯系统的机制，这导致HIV神经发病机制加剧，并同时促进HIV感染细胞的存活，从而形成病毒储存库。
