Baldridge J R, Pearce B D, Parekh B S, Buchmeier M J
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
Virology. 1993 Dec;197(2):669-77. doi: 10.1006/viro.1993.1642.
The effects of viral infection on the developing nervous system and the potential of passive immunotherapy to protect against infection were examined. When 4-day-old Lewis rats were injected intracerebrally with lymphocytic choriomeningitis virus (LCMV) the majority of stem cells within the external granular layer of the developing cerebellum became infected. The infection progressed to the molecular layer, internal granular layer, and the Purkinje cells. By 15 days postinfection the molecular and internal granular layers of LCMV-infected cerebella were noticeably thinner than those in the controls and the individual folia were smaller. Neurons remained infected for up to 40 days as determined by immunohistochemistry. However, in rats treated with rat monoclonal anti-LCMV antibodies the staining was limited to the cells of ependyma and choroid plexus and was not detectable by 15 days postinfection. Macroscopically the infection resulted in pronounced hypoplasia, with the cerebella of 21-day-old LCMV-infected rats weighing 52 +/- 10 mg compared with 159 +/- 30 mg for control rats. Antibody-treated rats exhibited normal cerebellar size and development. Neutralizing antibodies specific for the viral GP-1 glycoprotein were protective but nucleoprotein-specific antibodies were not. Furthermore, suckling rat pups born of and nursed by LCMV-immune mothers were spared from cerebellar disease following neonatal infection. These results suggest that passive immunotherapy of neonates can provide effective protection against teratogenic effects of neonatal viral infection on the developing CNS.
研究了病毒感染对发育中神经系统的影响以及被动免疫疗法预防感染的潜力。当给4日龄的Lewis大鼠脑内注射淋巴细胞性脉络丛脑膜炎病毒（LCMV）时，发育中小脑外颗粒层内的大多数干细胞被感染。感染进展到分子层、内颗粒层和浦肯野细胞。感染后15天，LCMV感染的小脑的分子层和内颗粒层明显比对照组薄，且单个小叶更小。通过免疫组织化学确定，神经元持续感染长达40天。然而，在用大鼠单克隆抗LCMV抗体治疗的大鼠中，染色仅限于室管膜和脉络丛细胞，感染后15天无法检测到。宏观上，感染导致明显的发育不全，21日龄LCMV感染大鼠的小脑重52±10mg，而对照大鼠为159±30mg。抗体治疗的大鼠小脑大小和发育正常。针对病毒GP-1糖蛋白的中和抗体具有保护作用，但针对核蛋白的抗体则没有。此外，由LCMV免疫的母亲生育并哺乳的乳鼠在新生儿感染后免于小脑疾病。这些结果表明，新生儿被动免疫疗法可以有效预防新生儿病毒感染对发育中中枢神经系统的致畸作用。
