Cell type-specific MxA-mediated inhibition of measles virus transcription in human brain cells
Cell type-specific MxA-mediated inhibition of measles virus transcription in human brain cells
复制标题
DOI：
10.1128/jvi.68.11.6910-6917.1994
复制
发表时间：
1994-11
影响因子：
5.4
通讯作者：
S. Schneider‐Schaulies;J. Schneider-Schaulies;Armin Schuster;M. Bayer;Jovana Lj. Pavlović;V. Meulen
中科院分区：
文献类型：
--
作者：
S. Schneider‐Schaulies;J. Schneider-Schaulies;Armin Schuster;M. Bayer;Jovana Lj. Pavlović;V. Meulen
麻疹病毒（MV）特异性转录在人脑细胞中的特征在于编码MV包膜蛋白的远端mRNA的丰度特别低。已经在组成型表达干扰素诱导型MxA蛋白的小鼠成纤维细胞中观察到密切相关的水疱性口炎病毒的类似转录限制（P. Staeheli和J. Pavlovic，J. Virol. 65：4498-4501，1991）。我们发现MV感染人脑细胞伴随着内源性MxA蛋白的快速诱导和高水平表达。稳定转染MxA后，人胶质母细胞瘤细胞（U-87-MxA）释放的感染性病毒减少了50至100倍，病毒蛋白的表达受到高度限制。总体MV特异性转录水平降低高达90%，伴随着远端MV特异性mRNA的相对频率较低。这些限制与病毒RNA合成的抑制有关，而与病毒RNA稳定性的降低无关。我们的研究结果表明，MxA的表达与MV在脑细胞中的转录衰减相关，因此可能有助于建立持续的MV中枢神经系统感染。此外，与水泡性口炎病毒的机制相反，MxA依赖性抗MV感染的机制是细胞类型特异性的，因为在MxA转染的人单核细胞中观察到MV糖蛋白合成的抑制与转录改变无关（J. J. Schnorr，S. Schneider-Schaulies，A.作者声明：J. A. Horisberger，and V. ter Meulen，J. Virol. 67：4760-4768，1993）。
Measles virus (MV)-specific transcription in human brain cells is characterized by particularly low abundances of the distal mRNAs encoding the MV envelope proteins. Similar transcriptional restrictions of the closely related vesicular stomatitis virus have been observed in mouse fibroblasts constitutively expressing the interferon-inducible MxA protein (P. Staeheli and J. Pavlovic, J. Virol. 65:4498-4501, 1991). We found that MV infection of human brain cells is accompanied by rapid induction and high-level expression of endogenous MxA proteins. After stable transfection of MxA, human glioblastoma cells (U-87-MxA) released 50- to 100-fold less infectious virus and expression of viral proteins was highly restricted. The overall MV-specific transcription levels were reduced by up to 90%, accompanied by low relative frequencies of the distal MV-specific mRNAs. These restrictions were linked to an inhibition of viral RNA synthesis and not to a decreased stability of the viral RNAs. Our results indicate that expression of MxA is associated with transcriptional attenuation of MV in brain cells, thus probably contributing to the establishment of persistent MV central nervous system infections. In addition, the mechanism of MxA-dependent resistance against MV infection, in contrast to that of vesicular stomatitis virus, is cell type specific, because an inhibition of MV glycoprotein synthesis independent of transcriptional alterations was observed in MxA-transfected human monocytes (J. J. Schnorr, S. Schneider-Schaulies, A. Simon-Jödicke, J. Pavlovic, M. A. Horisberger, and V. ter Meulen, J. Virol. 67: 4760-4768, 1993).