Orvedahl Anthony, Levine Beth
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell Microbiol. 2008 Sep;10(9):1747-56. doi: 10.1111/j.1462-5822.2008.01175.x. Epub 2008 May 22.
As terminally differentiated vital cells, neurons may be specialized to fight viral infections without undergoing cellular self-destruction. The cellular lysosomal degradation pathway, autophagy, is emerging as one such mechanism of neuronal antiviral defence. Autophagy has diverse physiological functions, such as cellular adaptation to stress, routine organelle and protein turnover, and innate immunity against intracellular pathogens, including viruses. Most of the in vivo evidence for an antiviral role of autophagy is related to viruses that specifically target neurons, including the prototype alphavirus, Sindbis virus, and the alpha-herpesvirus, herpes simplex virus type 1 (HSV-1). In the case of HSV-1, viral evasion of autophagy is essential for lethal encephalitis. As basal autophagy is important in preventing neurodegeneration, and induced autophagy is important in promoting cellular survival during stress, viral antagonism of autophagy in neurons may lead to neuronal dysfunction and/or neuronal cell death. This review provides background information on the roles of autophagy in immunity and neuroprotection, and then discusses the relationships between autophagy and viral neurovirulence.
作为终末分化的重要细胞，神经元可能专门用于对抗病毒感染而不发生细胞自我破坏。细胞溶酶体降解途径自噬，正成为神经元抗病毒防御的一种机制。自噬具有多种生理功能，如细胞对压力的适应、常规细胞器和蛋白质的更新，以及针对包括病毒在内的细胞内病原体的固有免疫。自噬抗病毒作用的大多数体内证据与特异性靶向神经元的病毒有关，包括原型甲病毒辛德毕斯病毒和甲型疱疹病毒单纯疱疹病毒1型（HSV-1）。就HSV-1而言，病毒对自噬的逃避对于致死性脑炎至关重要。由于基础自噬在预防神经退行性变中很重要，诱导自噬在应激期间促进细胞存活中很重要，神经元中自噬的病毒拮抗作用可能导致神经元功能障碍和/或神经元细胞死亡。本综述提供了自噬在免疫和神经保护中作用的背景信息，然后讨论了自噬与病毒神经毒力之间的关系。
