Griffin D E
Department of Molecular Microbiology and Immunology, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD 21205, USA.
Neurosci Biobehav Rev. 1998 Oct;22(6):721-3. doi: 10.1016/s0149-7634(98)00010-4.
Alphaviruses are important causes of mosquito-borne viral encephalitis. The prototype alphavirus, Sindbis virus, causes encephalomyelitis in mice. The primary target cell for nervous system infection is the neuron. Thus, Sindbis virus infection of mice provides a model system for studying virus-neuron interactions. The outcome of infection is dependent on the maturity of the targeted neurons and on the strain of Sindbis virus used for infection. Most Sindbis virus strains can induce programmed cell death or apoptosis in cultured lines of mammalian cells and in immature postmitotic neurons both in vitro and in vivo. As neurons mature they become increasingly resistant to Sindbis virus-induced apoptosis presumably due to increased expression with differentiation of cellular antiapoptotic proteins. Therefore, in the absence of an effective immune response, these relatively avirulent strains of Sindbis virus establish persistent nonfatal infection in mature neurons. More virulent strains of Sindbis virus can overcome this intrinsic resistance of mature neurons to apoptosis and cause neuronal death. Amino acid changes in the virion glycoproteins are the main determinants of neurovirulence and knowledge of the effects of specific changes allows the investigator to design Sindbis viruses of specified neurovirulence for animals of different ages.
甲病毒是蚊媒病毒性脑炎的重要病因。甲病毒的原型辛德毕斯病毒可在小鼠中引起脑脊髓炎。神经系统感染的主要靶细胞是神经元。因此，辛德毕斯病毒感染小鼠为研究病毒与神经元的相互作用提供了一个模型系统。感染的结果取决于靶神经元的成熟度以及用于感染的辛德毕斯病毒株。大多数辛德毕斯病毒株可在体外和体内诱导哺乳动物细胞系以及未成熟的有丝分裂后神经元发生程序性细胞死亡或凋亡。随着神经元成熟，它们对辛德毕斯病毒诱导的凋亡越来越有抵抗力，这可能是由于细胞抗凋亡蛋白随着分化而表达增加。因此，在缺乏有效免疫反应的情况下，这些相对无毒的辛德毕斯病毒株在成熟神经元中建立持续的非致命性感染。毒性更强的辛德毕斯病毒株可以克服成熟神经元对凋亡的这种内在抵抗力并导致神经元死亡。病毒粒子糖蛋白中的氨基酸变化是神经毒性的主要决定因素，了解特定变化的影响使研究人员能够为不同年龄的动物设计具有特定神经毒性的辛德毕斯病毒。
