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水痘-带状疱疹病毒 ORF11 基因产物的鉴定和功能特征分析。

Identification and functional characterization of the Varicella zoster virus ORF11 gene product.

机构信息

Departments of Pediatrics and Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.

出版信息

Virology. 2011 Mar 30;412(1):156-66. doi: 10.1016/j.virol.2010.12.055. Epub 2011 Jan 26.

Abstract

The deletion of ORF11 severely impaired VZV infection of human skin xenografts. Here, we investigate the characteristics and functions of the ORF11 gene product. ORF11 is expressed as a 118kDa polypeptide in VZV-infected cells; the protein is present in the nucleus and cytoplasm and is incorporated into VZ virions. Although ORF11 had little effect in transactivating VZV gene promoters in transfection assays, deleting ORF11 from the virus was associated with reduced expression of immediate early proteins IE4, IE62 and IE63, and the major glycoprotein, gE. ORF11 was identified as an RNA binding protein and its RNA binding domain was defined. However, disrupting the ORF11 RNA binding domain did not affect skin infection, indicating that RNA binding capacity, conserved among the alphaherpesviruses homologues, is not essential while the contribution of ORF11 to the expression of the IE proteins and gE may be required for VZV pathogenesis in skin in vivo.

摘要

ORF11 的缺失严重损害了 VZV 对人皮肤异种移植物的感染。在这里,我们研究了 ORF11 基因产物的特征和功能。ORF11 在感染 VZV 的细胞中表达为 118kDa 的多肽;该蛋白存在于细胞核和细胞质中,并被整合到 VZ 病毒粒子中。尽管 ORF11 在转染实验中对 VZV 基因启动子的转录激活几乎没有影响,但从病毒中删除 ORF11 与立即早期蛋白 IE4、IE62 和 IE63 以及主要糖蛋白 gE 的表达减少有关。ORF11 被鉴定为一种 RNA 结合蛋白,其 RNA 结合域被定义。然而,破坏 ORF11 RNA 结合域并不影响皮肤感染,这表明 RNA 结合能力在 α 疱疹病毒同源物中是保守的,在体内皮肤中对 VZV 发病机制而言并非必需,而 ORF11 对 IE 蛋白和 gE 的表达的贡献可能是必需的。

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