Sandberg K, Eloranta M L, Campbell I L
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
J Virol. 1994 Nov;68(11):7358-66. doi: 10.1128/JVI.68.11.7358-7366.1994.
Expression of alpha interferon (IFN-alpha)-, IFN-beta-, and IFN-alpha/beta-induced genes was monitored during the development of lymphocytic choriomeningitis (LCM) to assess whether a restricted influence of these antiviral cytokines could be found in the central nervous system (CNS). High levels of IFN-alpha (83 +/- 42 U/ml) were present in the blood of LCM virus-infected mice 3 days postinfection, whereas IFN-beta was not detected (< 1.0 U/ml) at any time point. Spleens contained high levels of IFN-alpha and IFN-beta mRNAs at days 1 and 3 postinfection, whereas no IFN-alpha mRNA and only low levels of IFN-beta mRNA were detected in brains. In situ hybridization showed IFN-alpha mRNA-expressing cells in the marginal zones of the spleen and in the subcapsular sinus and outer cortex of cervical lymph nodes. The expression of 2',5'-oligoadenylate synthetase (2',5'-OAS) mRNA followed the expression of IFN-beta mRNA in the brain, whereas 2',5'-OAS mRNA in the periphery was associated with systemic IFN-alpha. The localization of IFN-alpha-expressing cells in the spleen and lymph nodes in proximity to T- and B-cell compartments is consistent with a role for these cytokines in immune regulation. Furthermore, the absence of IFN-alpha and the relatively low level and delayed expression of IFN-beta in the brain suggest that the CNS is an especially vulnerable organ for virus replication. With certain strains of LCM virus, the absence of early antiviral IFN-alpha/beta activity and preferential virus growth in the brain might lead to targeted T-cell inflammation of the CNS, resulting in death of the animal.
在淋巴细胞性脉络丛脑膜炎（LCM）的发展过程中，监测了α干扰素（IFN-α）、IFN-β以及IFN-α/β诱导基因的表达，以评估在中枢神经系统（CNS）中是否能发现这些抗病毒细胞因子的有限影响。感染LCM病毒的小鼠在感染后3天血液中存在高水平的IFN-α（83±42 U/ml），而在任何时间点均未检测到IFN-β（<1.0 U/ml）。感染后第1天和第3天，脾脏中含有高水平的IFN-α和IFN-β mRNA，而在脑中未检测到IFN-α mRNA，仅检测到低水平的IFN-β mRNA。原位杂交显示，在脾脏边缘区以及颈部淋巴结的被膜下窦和外皮质中有表达IFN-α mRNA的细胞。2',5'-寡腺苷酸合成酶（2',5'-OAS）mRNA的表达在脑中与IFN-β mRNA的表达一致，而在外周，2',5'-OAS mRNA与全身的IFN-α相关。表达IFN-α的细胞在脾脏和淋巴结中靠近T细胞和B细胞区室的定位与这些细胞因子在免疫调节中的作用一致。此外，脑中缺乏IFN-α以及IFN-β水平相对较低且表达延迟表明，中枢神经系统是病毒复制的一个特别脆弱的器官。对于某些LCM病毒株，脑中缺乏早期抗病毒IFN-α/β活性以及病毒优先生长可能导致中枢神经系统发生靶向性T细胞炎症，从而导致动物死亡。
