Characterization of a potent varicella-zoster virus-encoded trans-repressor
Characterization of a potent varicella-zoster virus-encoded trans-repressor
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DOI：
10.1128/jvi.65.10.5289-5296.1991
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发表时间：
1991-10
影响因子：
5.4
通讯作者：
Sunil Nagpal;J. Ostrove
中科院分区：
文献类型：
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作者：
Sunil Nagpal;J. Ostrove
使用在Vero细胞中的瞬时表达试验，我们已经表明，水痘带状疱疹病毒（VZV）基因61的蛋白产物可以抑制VZV编码的反式激活因子对推定的病毒立即早期，早期和晚期基因启动子的功能。抑制作用在转录水平发挥，需要功能基因61蛋白。这种反式阻遏物是单纯疱疹1型ICP 0（一种反式激活因子）同源物，根据基因位置、氨基末端区域中富含半胱氨酸的推定锌结合指的共享以及有限的氨基酸同源性来定义。开放阅读框61（ORF 61）介导的反式阻遏似乎对VZV编码的反式激活因子具有特异性，因为它对猿猴病毒40和劳斯肉瘤病毒启动子没有影响。此外，它不抑制分别由tax和达特基因引起的人嗜T淋巴细胞病毒I型和人免疫缺陷病毒长末端重复序列的反式激活。我们构建了在ORF 61突变的质粒，并测试了它们抑制反式激活因子（VZV基因4和62）介导的病毒胸苷激酶启动子-氯霉素乙酰转移酶结构激活的能力。突变体含有中断的ORF 61失去了他们的反式阻遏能力，在蛋白质和稳态RNA水平证明。这些结果表明ORF 61蛋白产物可以介导VZV基因表达的下调。
Using a transient expression assay in Vero cells, we have shown that the protein product from gene 61 of varicella-zoster virus (VZV) can repress the function of the VZV encoded trans-activators on putative viral immediate-early, early, and late gene promoters. The repression is exerted at the transcriptional level and requires functional gene 61 protein. This trans-repressor is the herpes simplex type 1 ICP0 (a trans-activator) homolog, as defined by gene location, the sharing of a cysteine-rich putative zinc-binding finger in the amino-terminal region, and limited amino acid homology. Open reading frame 61 (ORF61)-mediated trans-repression appears to be specific for VZV-encoded trans-activators in that it has no effect on simian virus 40 and Rous sarcoma virus promoters. Moreover, it does not inhibit trans-activation of the human T-lymphotropic virus type I and human immunodeficiency virus long terminal repeats by tax and tat genes, respectively. We constructed plasmids with mutations in ORF61 and tested them for their ability to inhibit trans-activator (VZV genes 4 and 62)-mediated activation of the viral thymidine kinase promoter-chloramphenicol acetyltransferase construct. Mutants containing interruptions in ORF61 lost their trans-repressing ability, as demonstrated at both the protein and steady-state RNA levels. These results suggest that the ORF61 protein product can mediate down-regulation of VZV gene expression.