ACCUMULATED MEASLES-VIRUS MUTATIONS IN A CASE OF SUBACUTE SCLEROSING PANENCEPHALITIS - INTERRUPTED MATRIX PROTEIN READING FRAME AND TRANSCRIPTION ALTERATION
ACCUMULATED MEASLES-VIRUS MUTATIONS IN A CASE OF SUBACUTE SCLEROSING PANENCEPHALITIS - INTERRUPTED MATRIX PROTEIN READING FRAME AND TRANSCRIPTION ALTERATION
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DOI：
10.1016/0042-6822(86)90433-2
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发表时间：
1986-10-15
期刊：
影响因子：
3.7
通讯作者：
BILLETER, MA
中科院分区：
文献类型：
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作者：
CATTANEO, R;SCHMID, A;BILLETER, MA
亚急性硬化性全脑炎（SSPE）是一种在急性麻疹感染后数年内影响人中枢神经系统的致命疾病。麻疹病毒（MV）基因组在SSPE大脑中复制不会产生出芽颗粒，并且在基因表达方面存在各种缺陷，主要涉及基质(M)蛋白。对于一个SSPE病例(K)，先前显示缺乏M蛋白表达，我们在这里详细检查了与该缺陷相关的特征。在正常患者K的大脑中，单顺反子的MV - M mRNA完全被双顺反子RNA所取代，该双顺反子RNA除了含有M编码序列外，还含有前面磷酸化蛋白(P)基因的编码序列。通过直接cDNA测序对P-M顺反子间区进行分析，发现该RNA加工位点的一致序列没有改变，但发现了几个远点突变。对整个M编码区的cDNA克隆和测序证实，其中一个点突变导致M阅读框的三联体12处有一个停止密码子。目前尚不清楚这种缺陷是否也与M mRNA的形成受阻有关，它本身解释了M蛋白的缺乏。此外，我们注意到来自同一个大脑的两个重叠克隆之间有多达1%的核苷酸不同。这种高序列变异性可能解释了在SSPE大脑中观察到的MV基因表达缺陷的多样性，并且可能是与RNA病毒持久性相关的普遍现象。
Subacute sclerosing panencephalitis (SSPE) is a fatal disease affecting the human central nervous system several years after acute measles infection. Measles virus (MV) genomes replicating in SSPE brains do not give rise to budding particles and present various defects in gene expression, mostly concerning the matrix (M) protein. For one SSPE case (K), shown previously to be devoid of M protein expression, we examined here in detail the features involved in this defect. In the brain of patient K the normal, monocistronic MV M mRNA was completely substituted by a bicistronic RNA containing the coding sequence of the preceding phosphoprotein (P) gene in addition to the M coding sequence. Analysis of the P-M intercistronic region by direct cDNA sequencing showed that the consensus sequence at this RNA processing site was unaltered but revealed several distant point mutations. cDNA cloning and sequencing of the entire M coding region established that one of the point mutations leads to a stop codon at triplet 12 of the M reading frame. It is unknown whether this defect, explaining by itself the lack of M protein, is related also to the block of M mRNA formation. In addition we note that as much as 1% of the nucleotides differed between two overlapping clones from the same brain. This high sequence variability could possibly account for the diversity of defects observed in MV gene expression in SSPE brains and may be a general phenomenon associated with RNA virus persistence.