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单纯疱疹病毒 1 包膜蛋白及其 Epstein-Barr 病毒同源物的核输出综合分析。

Comprehensive analysis of nuclear export of herpes simplex virus type 1 tegument proteins and their Epstein-Barr virus orthologs.

机构信息

Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany.

Max von Pettenkofer-Institute, Ludwig-Maximilians-University Munich, Munich, Germany.

出版信息

Traffic. 2019 Feb;20(2):152-167. doi: 10.1111/tra.12627. Epub 2019 Jan 11.

DOI:10.1111/tra.12627
PMID:30548142
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6590417/
Abstract

Morphogenesis of herpesviral virions is initiated in the nucleus but completed in the cytoplasm. Mature virions contain more than 25 tegument proteins many of which perform both nuclear and cytoplasmic functions suggesting they shuttle between these compartments. While nuclear import of herpesviral proteins was shown to be crucial for viral propagation, active nuclear export and its functional impact are still poorly understood. To systematically analyze nuclear export of tegument proteins present in virions of Herpes simplex virus type 1 (HSV1) and Epstein-Barr virus (EBV), the Nuclear EXport Trapped by RAPamycin (NEX-TRAP) was applied. Nine of the 22 investigated HSV1 tegument proteins including pUL4, pUL7, pUL11, pUL13, pUL21, pUL37d11, pUL47, pUL48 and pUS2 as well as 2 out of 6 EBV orthologs harbor nuclear export activity. A functional leucine-rich nuclear export sequence (NES) recognized by the export factor CRM1/Xpo1 was identified in six of them. The comparison between experimental and bioinformatic data indicates that experimental validation of predicted NESs is required. Mutational analysis of the pUL48/VP16 NES revealed its importance for herpesviral propagation. Together our data suggest that nuclear export is an important feature of the herpesviral life cycle required to co-ordinate nuclear and cytoplasmic processes.

摘要

疱疹病毒病毒粒子的形态发生始于细胞核，但在细胞质中完成。成熟的病毒粒子包含超过 25 种包膜蛋白，其中许多蛋白具有核和细胞质功能，表明它们在这些隔室之间穿梭。虽然疱疹病毒蛋白的核输入被证明对病毒的繁殖至关重要，但活跃的核输出及其功能影响仍知之甚少。为了系统地分析单纯疱疹病毒 1 (HSV1) 和 Epstein-Barr 病毒 (EBV) 病毒粒子中存在的包膜蛋白的核输出，应用了雷帕霉素捕获的核输出 (NEX-TRAP)。在 22 种研究的 HSV1 包膜蛋白中，有 9 种（包括 pUL4、pUL7、pUL11、pUL13、pUL21、pUL37d11、pUL47、pUL48 和 pUS2）以及 6 种 EBV 同源物中的 2 种具有核输出活性。在其中 6 种蛋白中鉴定出了被输出因子 CRM1/Xpo1 识别的功能性亮氨酸丰富的核输出序列 (NES)。实验和生物信息学数据的比较表明，需要对预测的 NES 进行实验验证。对 pUL48/VP16 NES 的突变分析表明，它对疱疹病毒的繁殖很重要。我们的数据表明，核输出是疱疹病毒生命周期的一个重要特征，需要协调核和细胞质过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/eea5e766fc53/TRA-20-152-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/cc0eb2c6911f/TRA-20-152-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/0960f4a4d91e/TRA-20-152-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/c8506d5a570c/TRA-20-152-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/341a06b5e413/TRA-20-152-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/2b8646209319/TRA-20-152-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/eea5e766fc53/TRA-20-152-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/cc0eb2c6911f/TRA-20-152-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/0960f4a4d91e/TRA-20-152-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/c8506d5a570c/TRA-20-152-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/341a06b5e413/TRA-20-152-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/2b8646209319/TRA-20-152-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8072/6590417/eea5e766fc53/TRA-20-152-g004.jpg

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本文引用的文献

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