腺病毒E4orf3/4是一种在体外具有细胞转化特性的调节多肽

IF 4.7 Q1 VIROLOGY
Wing-Hang Ip, Luca D. Bertzbach, Thomas Speiseder, Thomas Dobner
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引用次数: 0

摘要

人类腺病毒C型5(HAdV-C5)早期区4(E4)编码几种不同的多肽,根据相应开放阅读框(ORF)的顺序和排列,定义为E4orf1至E4orf6/7。所有E4基因产物都通过与关键病毒和细胞调节蛋白的复杂相互作用网络运作,这些蛋白涉及转录、细胞凋亡、细胞周期控制和DNA修复。在这里,我们产生了一组在单个E4基因中携带点突变的病毒突变体。这些突变体的表型特征表明,这些ORF的突变对病毒复制没有或只有中等影响。即使是一个不能产生E4orf3、E4orf4和尚未表征的选择性剪接E4orf3/4融合蛋白的三重突变体,也在复制到野生型水平。E4orf3/4蛋白由E4orf3的N端33个氨基酸残基和E4orf4的C端28个氨基酸残基组成。有趣的是,我们发现,与E4orf3类似,E4orf3/4具有支持E1A/E1B诱导的原代啮齿动物细胞转化的特性。这些结果鉴定了E4orf3/4并对其进行了功能表征,并得出结论,E4orf3%4是另一种对病毒复制可有可无的E4区蛋白,但促进了E1A/E1B诱导的原代啮齿动物细胞的转化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The adenoviral E4orf3/4 is a regulatory polypeptide with cell transforming properties in vitro

The adenoviral E4orf3/4 is a regulatory polypeptide with cell transforming properties in vitro

The adenoviral E4orf3/4 is a regulatory polypeptide with cell transforming properties in vitro

The adenoviral E4orf3/4 is a regulatory polypeptide with cell transforming properties in vitro

The human adenovirus species C type 5 (HAdV-C5) early region 4 (E4) encodes several distinct polypeptides, defined as E4orf1 to E4orf6/7 according to the order and arrangement of the corresponding open reading frames (ORFs). All E4 gene products operate through a complex network of interactions with key viral and cellular regulatory proteins involved in transcription, apoptosis, cell cycle control, and DNA repair. Here, we generated a set of virus mutants carrying point mutations in the individual E4 genes. The phenotypic characterizations of these mutants revealed that mutations of these ORFs had no or only moderate effects on virus replication. Even a triple mutant that fails to produce E4orf3, E4orf4, and the yet uncharacterized alternatively spliced E4orf3/4 fusion protein, was replicating to wild type levels. The E4orf3/4 protein consists of the N-terminal 33 amino acid residues from E4orf3 and the C-terminal 28 amino acid residues from E4orf4. Intriguingly, we found that, similar to E4orf3, E4orf3/4 possesses properties that support the E1A/E1B-induced transformation of primary rodent cells. These results identify and functionally characterize E4orf3/4 and conclude that E4orf3/4 is another E4 region protein that is dispensable for virus replication but promotes the E1A/E1B-induced transformation of primary rodent cells.

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来源期刊
Tumour Virus Research
Tumour Virus Research Medicine-Infectious Diseases
CiteScore
6.50
自引率
2.30%
发文量
16
审稿时长
56 days
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