Department of Microbiology and Immunology, and Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana LA 71130-3932, USA.
Virology. 2011 Sep 1;417(2):430-42. doi: 10.1016/j.virol.2011.06.023. Epub 2011 Jul 26.
The equine herpesvirus 1 (EHV-1) negative regulatory IR2 protein (IR2P), an early 1,165-amino acid (aa) truncated form of the 1487-aa immediate-early protein (IEP), lacks the trans-activation domain essential for IEP activation functions but retains domains for binding DNA, TFIIB, and TBP and the nuclear localization signal. IR2P mutants of the N-terminal region which lack either DNA-binding activity or TFIIB-binding activity were unable to down-regulate EHV-1 promoters. In EHV-1-infected cells expressing full-length IR2P, transcription and protein expression of viral regulatory IE, early EICP0, IR4, and UL5, and late ETIF genes were dramatically inhibited. Viral DNA levels were reduced to 2.1% of control infected cells, but were vey weakly affected in cells that express the N-terminal 706 residues of IR2P. These results suggest that IR2P function requires the two N-terminal domains for binding DNA and TFIIB as well as the C-terminal residues 707 to 1116 containing the TBP-binding domain.
马疱疹病毒 1（EHV-1）负调控 IR2 蛋白（IR2P）是一种 1487 个氨基酸的即刻早期蛋白（IEP）的 1165 个氨基酸截断形式，缺乏激活 IEP 激活功能所必需的反式激活结构域，但保留了与 DNA、TFIIB 和 TBP 结合的结构域以及核定位信号。缺乏 DNA 结合活性或 TFIIB 结合活性的 N 端区域的 IR2P 突变体无法下调 EHV-1 启动子。在表达全长 IR2P 的 EHV-1 感染细胞中，病毒调节 IE、早期 EICP0、IR4 和 UL5 和晚期 ETIF 基因的转录和蛋白表达被显著抑制。病毒 DNA 水平降低至对照感染细胞的 2.1%，但在表达 IR2P 的 N 端 706 个残基的细胞中受到的影响非常弱。这些结果表明，IR2P 功能需要两个 N 端结构域结合 DNA 和 TFIIB 以及包含 TBP 结合结构域的 C 端 707 到 1116 个残基。
