Malik Shaily, Eugenin Eliseo A
Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, USA; Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, USA; Department of Microbiology, Biochemistry and Molecular Genetics, New Jersey Medical School, Rutgers University, Newark, NJ, USA.
Neurosci Lett. 2019 Mar 16;695:86-90. doi: 10.1016/j.neulet.2017.09.005. Epub 2017 Sep 5.
Neuron-Glia crosstalk is essential for efficient synaptic communication, cell growth and differentiation, neuronal activity, neurotransmitter recycling, and brain immune response. The master regulators of this neuron-glia communication are connexin containing Gap Junctions (GJs) and Hemichannels (HCs) as well as pannexin HCs. However, the role of these channels under pathological conditions, especially in infectious diseases is still in exploratory stages. Human Immunodeficiency Virus-1 (HIV) is one such infectious agent that takes advantage of the host intercellular communication systems, GJs and HCs, to exacerbate viral pathogenesis in the brain in spite of the antiretroviral therapy effectively controlling viral replication in the periphery. Although most infectious agents lead to total "shutdown" of gap junctional communication in parenchymal cells, HIV infection maintains and "hijacks" GJs and HCs to enable few infected cells to spread toxic intracellular agents to neighboring uninfected cells aggravating viral neuropathology even in the absence of viral replication. In this mini-review, we present a comprehensive overview of the role of GJs and HCs in augmenting HIV neuropathogenesis.
神经元与神经胶质细胞之间的相互作用对于高效的突触通讯、细胞生长与分化、神经元活动、神经递质循环以及大脑免疫反应至关重要。这种神经元 - 神经胶质细胞通讯的主要调节因子是含有缝隙连接（GJs）和半通道（HCs）的连接蛋白以及泛连接蛋白半通道。然而，这些通道在病理条件下，尤其是在传染病中的作用仍处于探索阶段。人类免疫缺陷病毒1型（HIV）就是这样一种感染因子，尽管抗逆转录病毒疗法能有效控制外周血中的病毒复制，但它仍利用宿主细胞间通讯系统——缝隙连接和半通道，加剧大脑中的病毒发病机制。尽管大多数感染因子会导致实质细胞间缝隙连接通讯完全“关闭”，但HIV感染会维持并“劫持”缝隙连接和半通道，使少数受感染细胞能够将有毒的细胞内物质传播到邻近未受感染细胞，即使在没有病毒复制的情况下也会加剧病毒性神经病理学。在这篇小型综述中，我们全面概述了缝隙连接和半通道在加剧HIV神经发病机制中的作用。
