The herpes simplex virus regulatory protein ICP27 contributes to the decrease in cellular mRNA levels during infection
The herpes simplex virus regulatory protein ICP27 contributes to the decrease in cellular mRNA levels during infection
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单纯疱疹病毒调节蛋白 ICP27 导致感染期间细胞 mRNA 水平下降
作者：
Mary Ann HARDWICKEt;R. Sandri
我们以前已经证明，单纯疱疹病毒立即早期调节蛋白ICP27在转录后影响mRNA的处理(R.M.Sandri-Goldin和G.E.Mendza，基因Dev。6：848-863,1992)。具体地说，在ICP27存在的情况下，用含有5‘或3’内含子的靶基因转染靶基因，剪接的靶mRNAs减少了5-10倍。在这里，我们研究了ICP27在单纯疱疹病毒1型(HSV-1)感染过程中对剪接细胞mRNAs积累的影响。ICP27病毒突变体已经被证明在宿主关闭方面是有缺陷的(W.R.Sack，C.C.Greene，D.P.Aschman，和P.A.Schaffer，J.Virol。55：796-805,1985)。因此，我们研究了ICP27是否可能通过影响宿主细胞的剪接而降低细胞mRNA水平，从而促进这一复杂的过程。研究发现，在ICP27缺陷的病毒突变体感染中，三种剪接宿主mRNAs的累积水平高于野生型HSV-1。核径流转录分析表明，差异发生在转录后。在野生型和ICP27变异病毒感染过程中，剪接产物的稳定性相似，在野生型HSV-1感染中检测到病毒剪接基因的未剪接前体mRNA，而在ICP27不表达的感染中检测到未剪接前体基因。这些结果表明，细胞mRNA水平的降低和前-mRNA的积累是相关的，并且可能是由宿主细胞剪接的损害引起的。这些数据进一步表明，这些效应的发生需要ICP27。
We have previously shown that the herpes simplex virus immediate-early regulatory protein ICP27 acts posttranscriptionally to affect mRNA processing (R. M. Sandri-Goldin and G. E. Mendoza, Genes Dev. 6:848-863, 1992). Specifically, in the presence of ICP27, spliced target mRNAs were decreased 5- to 10-fold in transfections with target genes containing a 5' or 3' intron. Here, we have investigated the effect of ICP27 during herpes simplex virus type 1 (HSV-1) infection on accumulation of spliced cellular mRNAs. ICP27 viral mutants have been shown to be defective in host shutoff (W. R. Sacks, C. C. Greene, D. P. Aschman, and P. A. Schaffer, J. Virol. 55:796-805, 1985). Therefore, we examined whether ICP27 could contribute to this complex process by decreasing cellular mRNA levels through its effects on host cell splicing. It was found that in infections with viral mutants defective in ICP27, the accumulated levels of three spliced host mRNAs were higher than those seen with wild-type HSV-1. The differences occurred posttranscriptionally as shown by nuclear runoff transcription assays. The stabilities of the spliced products during infection with wild-type or ICP27 mutant viruses were similar, and unspliced precursor mRNA for a viral spliced gene was detected in infections with wild-type HSV-1 but not in infections in which ICP27 was not expressed. These results suggest that the reduction in cellular mRNA levels and the accumulation of pre-mRNA are related and may be caused by an impairment in host cell splicing. These data further show that ICP27 is required for these effects to occur.
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含有质粒的单纯疱疹病毒 1 型 α 基因可以抑制 CV-1 中 α 启动子调节的表达，但不能抑制 HeLa 细胞。
影响因子：
5
作者：
Block,T;Jordan,R
通讯作者：
Jordan,R
影响因子：
10.5
作者：
SANDRIGOLDIN, RM;MENDOZA, GE
通讯作者：
MENDOZA, GE
单纯疱疹病毒α蛋白ICP27可以抑制或增强病毒基因反式激活。
影响因子：
3.7
作者：
Su,L;Knipe,DM
通讯作者：
Knipe,DM
DOI：
10.1073/pnas.84.7.1926
发表时间：
1987-04-01
影响因子：
11.1
作者：
KWONG, AD;FRENKEL, N
通讯作者：
FRENKEL, N
DOI：
10.1089/dna.1983.2.329
发表时间：
1983-01-01
期刊：
DNA-A JOURNAL OF MOLECULAR & CELLULAR BIOLOGY
影响因子：
--
作者：
CATHALA, G;SAVOURET, JF;BAXTER, JD
通讯作者：
BAXTER, JD