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转基因模型中的麻疹病毒感染:病毒诱导的免疫抑制和中枢神经系统疾病。

Measles virus infection in a transgenic model: virus-induced immunosuppression and central nervous system disease.

作者信息

Oldstone M B, Lewicki H, Thomas D, Tishon A, Dales S, Patterson J, Manchester M, Homann D, Naniche D, Holz A

机构信息

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.

出版信息

Cell. 1999 Sep 3;98(5):629-40. doi: 10.1016/s0092-8674(00)80050-1.

Abstract

Measles virus (MV) infects 40 million persons and kills one million per year primarily by suppressing the immune system and afflicting the central nervous system (CNS). The lack of a suitable small animal model has impeded progress of understanding how MV causes disease and the development of novel therapies and improved vaccines. We tested a transgenic mouse line in which expression of the MV receptor CD46 closely mimicked the location and amount of CD46 found in humans. Virus replicated in and was recovered from these animals' immune systems and was associated with suppression of humoral and cellular immune responses. Infectious virus was recovered from the CNS, replicated primarily in neurons, and spread to distal sites presumably by fast axonal transport. Thus, a small animal model is available for analysis of MV pathogenesis.

摘要

麻疹病毒(MV)每年感染4000万人并导致100万人死亡,主要是通过抑制免疫系统和侵害中枢神经系统(CNS)。缺乏合适的小动物模型阻碍了对MV致病机制的理解以及新型疗法和改良疫苗的研发进展。我们测试了一种转基因小鼠品系,其中MV受体CD46的表达与人类中发现的CD46的位置和数量极为相似。病毒在这些动物的免疫系统中复制并从中恢复,且与体液和细胞免疫反应的抑制有关。从CNS中恢复了传染性病毒,其主要在神经元中复制,并可能通过快速轴突运输扩散到远端部位。因此,有了一个用于分析MV发病机制的小动物模型。

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