BIASED HYPERMUTATION AND OTHER GENETIC CHANGES IN DEFECTIVE MEASLES VIRUSES IN HUMAN-BRAIN INFECTIONS
BIASED HYPERMUTATION AND OTHER GENETIC CHANGES IN DEFECTIVE MEASLES VIRUSES IN HUMAN-BRAIN INFECTIONS
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DOI：
10.1016/0092-8674(88)90048-7
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发表时间：
1988-10-21
期刊：
影响因子：
64.5
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
我们从两名亚急性硬化性泛脑炎患者和一名麻疹包涵体脑炎(MIBE)患者的脑尸检中克隆了麻疹病毒(MV)基因的全长转录本，以评估持续感染时病毒基因表达的变化。这些MV基因的序列分析表明，在持续期间，几乎2%的核苷酸发生了突变，其中35%的差异导致了氨基酸的变化。其中一个核苷酸替换和一个缺失导致了两个融合基因阅读框的改变，合成的mRNAs的体外翻译证实了这一点。有一组突变是例外的；在Mibe病例的基质基因中，50%的U残基被改变为C，这可能是由于高度偏见的复制事件专门影响该基因造成的。我们认为，MIBE病例中的突变簇，以及其他病例中的其他突变组合，通过赋予突变的基因组选择性优势，有利于MV感染在脑细胞中的传播。
We assessed the alterations of viral gene expression occurring persistent infections by cloning full-length transcripts of measles virus (MV) genes from brain autopsies of two subacute sclerosing panencephalitis patients and one measles inclusion body encephalitis (MIBE) patient. The sequence of these MV genes revealed that, most likely, almost 2% of the nucleotides were mutated during persistence, and 35% of these differences resulted in amino acid changes. One of these nucleotide substitutions and one deletion resulted in alteration of the reading frames of two fusion genes, as confirmed by in vitro translation of synthetic mRNAs. One cluster of mutations was exceptional; in the matrix gene of the MIBE case, 50% of the U residues were changed to C, which might result from a highly biased copying event exclusively affecting this gene. We propose that the cluster of mutations in the MIBE cases, and other combinations of mutations in other cases, favored propagation of MV infections in brain cells by conferring a selective advantage to the mutated genomes.