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鸟苷酸结合蛋白2发挥依赖于GTP酶的抗埃可病毒作用。

Guanylate-Binding Protein 2 Exerts GTPase-Dependent Anti-Ectromelia Virus Effect.

作者信息

Gao Zhenzhen, Meng Zejing, He Xiaobing, Chen Guohua, Fang Yongxiang, Tian Huihui, Zhang Hui, Jing Zhizhong

机构信息

State Key Laboratory for Animal Disease Control and Prevention, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.

Ministry of Agriculture Key Laboratory of Veterinary Public Health, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.

出版信息

Microorganisms. 2023 Sep 8;11(9):2258. doi: 10.3390/microorganisms11092258.

DOI:10.3390/microorganisms11092258
PMID:37764102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10534507/
Abstract

Guanylate-binding proteins (GBPs) are highly expressed interferon-stimulated genes (ISGs) that play significant roles in protecting against invading pathogens. Although their functions in response to RNA viruses have been extensively investigated, there is limited information available regarding their role in DNA viruses, particularly poxviruses. Ectromelia virus (ECTV), a member of the orthopoxvirus genus, is a large double-stranded DNA virus closely related to the monkeypox virus and variola virus. It has been intensively studied as a highly effective model virus. According to the study, GBP2 overexpression suppresses ECTV replication in a dose-dependent manner, while GBP2 knockdown promotes ECTV infection. Additionally, it was discovered that GBP2 primarily functions through its N-terminal GTPase activity, and the inhibitory effect of GBP2 was disrupted in the GTP-binding-impaired mutant GBP2. This study is the first to demonstrate the inhibitory effect of GBP2 on ECTV, and it offers insights into innovative antiviral strategies.

摘要

鸟苷酸结合蛋白（GBPs）是高度表达的干扰素刺激基因（ISGs），在抵御入侵病原体方面发挥着重要作用。尽管它们在应对RNA病毒中的功能已得到广泛研究，但关于它们在DNA病毒，特别是痘病毒中的作用的信息有限。痘苗病毒属的成员埃可病毒（ECTV）是一种大型双链DNA病毒，与猴痘病毒和天花病毒密切相关。它作为一种高效的模型病毒已得到深入研究。根据该研究，GBP2的过表达以剂量依赖的方式抑制ECTV复制，而GBP2的敲低则促进ECTV感染。此外，还发现GBP2主要通过其N端GTPase活性发挥作用，并且在GTP结合受损的突变体GBP2中，GBP2的抑制作用被破坏。这项研究首次证明了GBP2对ECTV的抑制作用，并为创新的抗病毒策略提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/01810a6ec494/microorganisms-11-02258-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/f555c6d29d25/microorganisms-11-02258-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/cac27cf0e50b/microorganisms-11-02258-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/2c28a1005928/microorganisms-11-02258-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/c56c60085598/microorganisms-11-02258-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/01810a6ec494/microorganisms-11-02258-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/f555c6d29d25/microorganisms-11-02258-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/cac27cf0e50b/microorganisms-11-02258-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/2c28a1005928/microorganisms-11-02258-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/c56c60085598/microorganisms-11-02258-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ceff/10534507/01810a6ec494/microorganisms-11-02258-g005.jpg

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本文引用的文献

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Functional cross-species conservation of guanylate-binding proteins in innate immunity.先天免疫中鸟苷酸结合蛋白的功能跨物种保守性。
Med Microbiol Immunol. 2023 Apr;212(2):141-152. doi: 10.1007/s00430-022-00736-7. Epub 2022 Apr 13.
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Comparative Pathogenesis, Genomics and Phylogeography of Mousepox.鼠痘的比较发病机制、基因组学和系统地理学研究
The Viral Protein Poly(A) Polymerase Catalytic Subunit Interacts with Guanylate-Binding Proteins 2 to Antagonize the Antiviral Ability of Targeting Ectromelia Virus.
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Int J Mol Sci. 2023 Oct 30;24(21):15750. doi: 10.3390/ijms242115750.
Viruses. 2021 Jun 15;13(6):1146. doi: 10.3390/v13061146.
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Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins.G 蛋白结合蛋白的 GTP 诱导二聚化和抗病毒功能的结构基础。
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When human guanylate-binding proteins meet viral infections.当人类鸟苷酸结合蛋白遇到病毒感染时。
J Biomed Sci. 2021 Mar 5;28(1):17. doi: 10.1186/s12929-021-00716-8.
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