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[巨细胞病毒感染的成纤维细胞中人类2',5'-寡腺苷酸合成酶基因活性的调控]

[Regulation of human fibrolastic 2',5'-oligoadenylate synthetase gene activity in cytomegalovirus infected fibroblast cells].

作者信息

Sokolova T M, Fedorova N E, Medzhidova M G, Terekhov S M, Uryvaev L V, Kushch A A

出版信息

Vopr Virusol. 2007 Jan-Feb;52(1):28-36.

PMID:17338231
Abstract

Great differences were found in the level of 2',5'-oligoadenylate synthetase 40-46 kDa (OAS1) mRNA in relation to the proliferative state of human diploid fibroblasts at the moment of cytomegalovirus (CMV) (the strain AD169) infection. In the phase of synthesis of cellular cycle DNA (S), CMV induced OAS1 mRNA transcription by 10-100 times stronger than then in phase Go infection. The level of viral induction OAS1 mRNA peaked by hour 12 postinfection. The high gene activity correlated with suppressed DNA synthesis, a slowing-down mitotic cycle, markedly inhibited CMV replication, and delayed cell death. When the cells were infected in phase Go, the stimulation of OAS1 gene activity was less and it was attended by intensive viral replication and rapid cell death. There was a direct relationship between the resistance of cells and the constitutive level of OAS1 gene expression: in the low CMV-sensitive cells, the activity of OAS1 gene was more than 10 times greater than that in the highly sensitive cells. The inhibitors of the enzymatic OAS activity induced by IFN and dsRNA were found in the cytoplasm of the CMV-infected cells.

摘要

在巨细胞病毒(CMV,AD169株)感染时,发现2',5'-寡腺苷酸合成酶40 - 46 kDa(OAS1)mRNA水平与人类二倍体成纤维细胞的增殖状态存在巨大差异。在细胞周期DNA合成期(S期),CMV诱导OAS1 mRNA转录的强度比在G0期感染时强10 - 100倍。病毒诱导OAS1 mRNA的水平在感染后12小时达到峰值。高基因活性与DNA合成受抑制、有丝分裂周期减慢、CMV复制明显受抑制以及细胞死亡延迟相关。当细胞在G0期被感染时,OAS1基因活性的刺激较小,同时伴有强烈的病毒复制和快速的细胞死亡。细胞的抗性与OAS1基因表达的组成水平之间存在直接关系:在低CMV敏感性细胞中,OAS1基因的活性比高敏感性细胞高10倍以上。在CMV感染细胞的细胞质中发现了由IFN和dsRNA诱导的OAS酶活性抑制剂。

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