UL49是病毒前起始复合物的一个必需亚基，该复合物调节人类巨细胞病毒基因转录。

UL49 is an essential subunit of the viral pre-initiation complex that regulates human cytomegalovirus gene transcription.

作者信息

Turner Declan L, Fritzlar Svenja, Sadeghipour Sara, Barugahare Adele A, Russ Brendan E, Turner Stephen J, Mathias Rommel A

机构信息

Infection and Immunity Program, Monash Biomedicine Discovery Institute, and Department of Microbiology, Monash University, 23 Innovation Walk, Clayton, VIC 3800, Australia.

Monash Bioinformatics Platform, Monash University, Clayton, VIC 3800, Australia.

出版信息

iScience. 2022 Sep 19;25(10):105168. doi: 10.1016/j.isci.2022.105168. eCollection 2022 Oct 21.

DOI:10.1016/j.isci.2022.105168

PMID:36204275

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9530030/

Abstract

More than half the world's population is infected with human cytomegalovirus (HCMV), causing congenital birth defects and impacting the immuno-compromised. Many of the >170 HCMV genes remain uncharacterized, and this gap in knowledge limits the development of novel antivirals. In this study, we investigated the essential viral protein UL49 and found it displayed leaky late expression kinetics, and localized to nuclear replication compartments. Cells infected with mutant UL49 virus were unable to produce infectious virions and phenocopied other beta-gamma viral pre-initiation complex (vPIC) subunit (UL79, UL87, UL91, UL92, and UL95) mutant infections. RNA-seq analysis of vPIC mutant infections revealed a consistent diminution of genes encoding capsid subunits, including TRX2/UL85 and MCP/UL86, envelope glycoproteins gM, gL and gO, and egress-associated tegument proteins UL99 and UL103. Therefore, as a member of the vPIC, UL49 serves as a fundamental HCMV effector that governs viral gene transcription required to complete the replication cycle.

摘要

全球超过一半的人口感染了人巨细胞病毒（HCMV），该病毒会导致先天性出生缺陷并影响免疫功能低下者。170多种HCMV基因中的许多基因仍未得到表征，这一知识空白限制了新型抗病毒药物的开发。在本研究中，我们研究了必需的病毒蛋白UL49，发现它表现出渗漏性晚期表达动力学，并定位于核复制区室。感染突变型UL49病毒的细胞无法产生感染性病毒粒子，并且其表型与其他β-γ病毒前起始复合物（vPIC）亚基（UL79、UL87、UL91、UL92和UL95）突变感染相似。对vPIC突变感染的RNA测序分析显示，编码衣壳亚基（包括TRX2/UL85和MCP/UL86）、包膜糖蛋白gM、gL和gO以及与出芽相关的被膜蛋白UL99和UL103的基因一致减少。因此，作为vPIC的一员，UL49是一种基本的HCMV效应因子，它控制着完成复制周期所需的病毒基因转录。