气候变化领域集成服务门户(CCPortal): Herpesvirus-mediated stabilization of ICP0 expression neutralizes restriction by TRIM23

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DOI	10.1073/pnas.2113060118
	Herpesvirus-mediated stabilization of ICP0 expression neutralizes restriction by TRIM23
	Liu X.; Acharya D.; Krawczyk E.; Kangas C.; Gack M.U.; He B.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:51
英文摘要	Herpes simplex virus (HSV) infection relies on immediate early proteins that initiate viral replication. Among them, ICP0 is known, for many years, to facilitate the onset of viral gene expression and reactivation from latency. However, how ICP0 itself is regulated remains elusive. Through genetic analyses, we identify that the viral γ134.5 protein, an HSV virulence factor, interacts with and prevents ICP0 from proteasomal degradation. Furthermore, we show that the host E3 ligase TRIM23, recently shown to restrict the replication of HSV-1 (and certain other viruses) by inducing autophagy, triggers the proteasomal degradation of ICP0 via K11- and K48-linked ubiquitination. Functional analyses reveal that the γ134.5 protein binds to and inactivates TRIM23 through blockade of K27-linked TRIM23 autoubiquitination. Deletion of γ134.5 or ICP0 in a recombinant HSV-1 impairs viral replication, whereas ablation of TRIM23 markedly rescues viral growth. Herein, we show that TRIM23, apart from its role in autophagy-mediated HSV-1 restriction, down-regulates ICP0, whereas viral γ134.5 functions to disable TRIM23. Together, these results demonstrate that posttranslational regulation of ICP0 by virus and host factors determines the outcome of HSV-1 infection. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Gene expression; Herpes simplex virus; TRIM23; Viral replication; Virus–host interaction
语种	英语
scopus关键词	guanine nucleotide binding protein; immediate early protein; TBK1 protein, human; TRIM23 protein, human; ubiquitin protein ligase; virus antibody; Vmw110 protein, Human herpesvirus 1; animal; cell line; gene expression regulation; genetics; host pathogen interaction; human; Human alphaherpesvirus 1; metabolism; physiology; virus replication; Animals; Antibodies, Viral; Cell Line; Gene Expression Regulation, Viral; GTP-Binding Proteins; Herpesvirus 1, Human; Host-Pathogen Interactions; Humans; Immediate-Early Proteins; Protein Serine-Threonine Kinases; Ubiquitin-Protein Ligases; Virus Replication
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/250910
作者单位	Department of Microbiology and Immunology, University of Illinois, College of Medicine, Chicago, IL 60612, United States; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, United States
推荐引用方式 GB/T 7714	Liu X.,Acharya D.,Krawczyk E.,et al. Herpesvirus-mediated stabilization of ICP0 expression neutralizes restriction by TRIM23[J],2021,118(51).
APA	Liu X.,Acharya D.,Krawczyk E.,Kangas C.,Gack M.U.,&He B..(2021).Herpesvirus-mediated stabilization of ICP0 expression neutralizes restriction by TRIM23.Proceedings of the National Academy of Sciences of the United States of America,118(51).
MLA	Liu X.,et al."Herpesvirus-mediated stabilization of ICP0 expression neutralizes restriction by TRIM23".Proceedings of the National Academy of Sciences of the United States of America 118.51(2021).