Herpes simplex virus alpha protein ICP27 can inhibit or augment viral gene transactivation.

Herpes simplex virus alpha protein ICP27 can inhibit or augment viral gene transactivation.
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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。

DOI:
10.1016/0042-6822(89)90441-8
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发表时间:
1989
期刊:
影响因子:
3.7
通讯作者:
Knipe,DM
Knipe,DM
中科院分区:
医学3区
文献类型:
--
作者:
Su,L;Knipe,DM

文献摘要

被引文献

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单纯疱疹病毒的5种α(立即早期)基因产物中的3种,感染细胞蛋白(ICP)4、0和27在控制病毒β(延迟早期)和γ(晚期)基因的表达中起作用。我们在这里报告,ICP27可以抑制或增强ICP4和ICPO的单独或组合的能力,以刺激含有病毒基因启动子的嵌合基因在瞬时表达系统中的表达。ICP27的特异性作用依赖于嵌合基因中的病毒基因启动子。ICP27抑制ICP4和ICPO激活某些γ基因启动子的能力,但当它们用于靶基因时,增强它们激活其它β或γ1基因启动子的能力。在相同条件下,ICP27不影响腺病毒ElA对靶基因的激活。ICP27还抑制ICPO刺激含有α基因启动子的嵌合基因表达的能力。在ICP27编码区中间插入终止密码子严重降低了质粒的抑制作用,表明该活性需要功能性ICP27多肽的表达。本报告重点关注ICP27活性,该活性负调节含有HSV β基因ICP8上游序列的嵌合基因的ICP4反式激活。ICP27降低了ICP8基因转录起始位点的mRNA水平。ICP27没有改变ICP4基因的表达水平,但观察到表达的ICP4的电泳迁移率改变。ICP27对HSV反式激活因子的调节作用可能控制裂解周期的进展或提供改变不同细胞类型的平衡,以影响裂解或潜伏感染是否发生。
Three of the five α (immediate early) gene products of herpes simplex virus, infected cell proteins (ICPs) 4, 0, and 27 play a role in the control of expression of viral β (delayed-early) and γ (late) genes. We report here that ICP27 can inhibit or augment the individual or combined abilities of ICP4 and ICPO to stimulate expression of chimeric genes containing viral gene promoters in a transient expression system. The specific effect of ICP27 was dependent on the viral gene promoter in the chimeric gene. ICP27 inhibited the ability of ICP4 and ICPO to activate some ,γ gene promoters but augmented their ability to activate other β or γ1 gene promoters when they were used in the target genes. Activation of the target genes by adenovirus ElA was not affected by ICP27 under the same conditions. ICP27 also repressed the ability of ICPO to stimulate expression of a chimeric gene containing an a gene promoter. Insertion of a termination codon in the middle of the ICP27 coding region severely reduced the inhibitory effect of the plasmid, indicating that this activity requires expression of functional ICP27 polypeptide. This report focuses on the ICP27 activity that negatively regulates ICP4 transactivation of a chimeric gene containing the upstream sequences of the HSV β gene ICP8. ICP27 decreased the level of mRNA initiated at the transcriptional start site of the ICP8 gene. The level of expression of the ICP4 gene was not changed by ICP27 but an alteration in the electrophoretic mobility of ICP4 expressed was observed. The modulatory effect of ICP27 on HSV transactivators may control the progress of the lytic cycle or provide a balance that varies indifferent cell types to affect whether lytic or latent infection ensues.