一种可规避对III类β型磷脂酰肌醇4激酶需求的柯萨奇病毒突变体的适应性和毒力
Fitness and virulence of a coxsackievirus mutant that can circumnavigate the need for phosphatidylinositol 4-kinase class III beta.
作者信息
Thibaut Hendrik Jan, van der Schaar Hilde M, Lanke Kjerstin H W, Verbeken Erik, Andrews Martin, Leyssen Pieter, Neyts Johan, van Kuppeveld Frank J M
机构信息
Department of Infectious Diseases & Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
出版信息
J Virol. 2014 Mar;88(5):3048-51. doi: 10.1128/JVI.03177-13. Epub 2013 Dec 26.
Abstract
Coxsackieviruses require phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) for replication but can bypass this need by an H57Y mutation in protein 3A (3A-H57Y). We show that mutant coxsackievirus is not outcompeted by wild-type virus during 10 passages in vitro. In mice, the mutant virus proved as virulent as wild-type virus, even when mice were treated with a PI4KIIIβ inhibitor. Our data suggest that upon emergence, the 3A-H57Y mutant has the fitness to establish a resistant population with a virulence similar to that of wild-type virus.
摘要
柯萨奇病毒的复制需要磷脂酰肌醇-4-激酶IIIβ（PI4KIIIβ），但可通过蛋白3A中的H57Y突变（3A-H57Y）绕过这一需求。我们发现，在体外传代10次的过程中，突变型柯萨奇病毒不会被野生型病毒淘汰。在小鼠中，即使给小鼠使用PI4KIIIβ抑制剂，突变病毒也与野生型病毒一样具有毒性。我们的数据表明，3A-H57Y突变体一旦出现，就具备形成一个与野生型病毒毒力相似的抗性群体的适应性。
相似文献
1
Fitness and virulence of a coxsackievirus mutant that can circumnavigate the need for phosphatidylinositol 4-kinase class III beta.一种可规避对III类β型磷脂酰肌醇4激酶需求的柯萨奇病毒突变体的适应性和毒力
J Virol. 2014 Mar;88(5):3048-51. doi: 10.1128/JVI.03177-13. Epub 2013 Dec 26.
2
Modulation of proteolytic polyprotein processing by coxsackievirus mutants resistant to inhibitors targeting phosphatidylinositol-4-kinase IIIβ or oxysterol binding protein.柯萨奇病毒突变体对针对磷脂酰肌醇-4-激酶 IIIβ或氧化固醇结合蛋白的抑制剂的抗性对蛋白水解多蛋白加工的调节。
Antiviral Res. 2017 Nov;147:86-90. doi: 10.1016/j.antiviral.2017.10.006. Epub 2017 Oct 9.
3
Recruitment of PI4KIIIβ to coxsackievirus B3 replication organelles is independent of ACBD3, GBF1, and Arf1.PI4KIIIβ募集至柯萨奇病毒B3复制细胞器的过程独立于ACBD3、GBF1和Arf1。
J Virol. 2014 Mar;88(5):2725-36. doi: 10.1128/JVI.03650-13. Epub 2013 Dec 18.
4
A novel, broad-spectrum inhibitor of enterovirus replication that targets host cell factor phosphatidylinositol 4-kinase IIIβ.一种新型的、广谱的肠道病毒复制抑制剂，靶向宿主细胞因子磷脂酰肌醇 4-激酶 IIIβ。
Antimicrob Agents Chemother. 2013 Oct;57(10):4971-81. doi: 10.1128/AAC.01175-13. Epub 2013 Jul 29.
5
Coxsackievirus mutants that can bypass host factor PI4KIIIβ and the need for high levels of PI4P lipids for replication.能够绕过宿主因子 PI4KIIIβ 和高水平 PI4P 脂质复制需求的柯萨奇病毒突变体。
Cell Res. 2012 Nov;22(11):1576-92. doi: 10.1038/cr.2012.129. Epub 2012 Sep 4.
6
New small-molecule inhibitors effectively blocking picornavirus replication.新型小分子抑制剂能有效阻断微小核糖核酸病毒复制。
J Virol. 2014 Oct;88(19):11091-107. doi: 10.1128/JVI.01877-14. Epub 2014 Jul 9.
7
ACBD3 Is an Essential Pan-enterovirus Host Factor That Mediates the Interaction between Viral 3A Protein and Cellular Protein PI4KB.ACBD3 是一种必需的泛肠孤病毒宿主因子，介导病毒 3A 蛋白与细胞蛋白 PI4KB 之间的相互作用。
mBio. 2019 Feb 12;10(1):e02742-18. doi: 10.1128/mBio.02742-18.
8
Phosphatidylinositol 4-kinase III beta is a target of enviroxime-like compounds for antipoliovirus activity.磷脂酰肌醇 4-激酶 IIIβ是抗脊髓灰质炎病毒活性类似依维莫司化合物的靶标。
J Virol. 2011 Mar;85(5):2364-72. doi: 10.1128/JVI.02249-10. Epub 2010 Dec 22.
9
Identification of a nucleotide in 5' untranslated region contributing to virus replication and virulence of Coxsackievirus A16.鉴定5'非翻译区中一个有助于柯萨奇病毒A16复制和毒力的核苷酸。
Sci Rep. 2016 Feb 10;6:20839. doi: 10.1038/srep20839.
10
Essential domains of phosphatidylinositol-4 kinase III β required for enterovirus replication.肠道病毒复制所需的磷脂酰肌醇-4激酶IIIβ的必需结构域。
Microbiol Immunol. 2019 Jul;63(7):285-288. doi: 10.1111/1348-0421.12718. Epub 2019 Jun 27.
引用本文的文献
1
The multifaceted role of the viral 2A protease in enterovirus replication and antagonism of host antiviral responses.病毒2A蛋白酶在肠道病毒复制及宿主抗病毒反应拮抗中的多方面作用
PLoS Pathog. 2025 Aug 28;21(8):e1013443. doi: 10.1371/journal.ppat.1013443. eCollection 2025 Aug.
2
Enterovirus Replication Organelles and Inhibitors of Their Formation.肠道病毒复制细胞器及其形成抑制剂
Front Microbiol. 2020 Aug 20;11:1817. doi: 10.3389/fmicb.2020.01817. eCollection 2020.
3
A large scale high-throughput screen identifies chemical inhibitors of phosphatidylinositol 4-kinase type II alpha.大规模高通量筛选鉴定出磷脂酰肌醇 4-激酶 IIα 的化学抑制剂。
J Lipid Res. 2019 Mar;60(3):683-693. doi: 10.1194/jlr.D090159. Epub 2019 Jan 9.
4
Enterovirus 3A Facilitates Viral Replication by Promoting Phosphatidylinositol 4-Kinase IIIβ-ACBD3 Interaction.肠道病毒3A通过促进磷脂酰肌醇4激酶IIIβ与ACBD3的相互作用来促进病毒复制。
J Virol. 2017 Sep 12;91(19). doi: 10.1128/JVI.00791-17. Print 2017 Oct 1.
5
The Golgi protein ACBD3 facilitates Enterovirus 71 replication by interacting with 3A.高尔基蛋白 ACBD3 通过与 3A 相互作用促进肠道病毒 71 的复制。
Sci Rep. 2017 Mar 17;7:44592. doi: 10.1038/srep44592.
6
Fat(al) attraction: Picornaviruses Usurp Lipid Transfer at Membrane Contact Sites to Create Replication Organelles.致命吸引力：小核糖核酸病毒在膜接触位点篡夺脂质转运以形成复制细胞器
Trends Microbiol. 2016 Jul;24(7):535-546. doi: 10.1016/j.tim.2016.02.017. Epub 2016 Mar 22.
7
Ultrastructure of the replication sites of positive-strand RNA viruses.正链RNA病毒复制位点的超微结构
Virology. 2015 May;479-480:418-33. doi: 10.1016/j.virol.2015.02.029. Epub 2015 Mar 6.
8
Rewiring of cellular membrane homeostasis by picornaviruses.微小核糖核酸病毒对细胞膜稳态的重塑
J Virol. 2014 Sep 1;88(17):9478-89. doi: 10.1128/JVI.00922-14. Epub 2014 Jun 11.
本文引用的文献
1
A novel, broad-spectrum inhibitor of enterovirus replication that targets host cell factor phosphatidylinositol 4-kinase IIIβ.一种新型的、广谱的肠道病毒复制抑制剂，靶向宿主细胞因子磷脂酰肌醇 4-激酶 IIIβ。
Antimicrob Agents Chemother. 2013 Oct;57(10):4971-81. doi: 10.1128/AAC.01175-13. Epub 2013 Jul 29.
2
Coxsackievirus mutants that can bypass host factor PI4KIIIβ and the need for high levels of PI4P lipids for replication.能够绕过宿主因子 PI4KIIIβ 和高水平 PI4P 脂质复制需求的柯萨奇病毒突变体。
Cell Res. 2012 Nov;22(11):1576-92. doi: 10.1038/cr.2012.129. Epub 2012 Sep 4.
3
Phosphatidylinositol 4-kinase III beta is a target of enviroxime-like compounds for antipoliovirus activity.磷脂酰肌醇 4-激酶 IIIβ是抗脊髓灰质炎病毒活性类似依维莫司化合物的靶标。
J Virol. 2011 Mar;85(5):2364-72. doi: 10.1128/JVI.02249-10. Epub 2010 Dec 22.
4
A bifunctional anti-enterovirus compound that inhibits replication and the early stage of enterovirus 71 infection.一种具有双重功能的抗肠道病毒化合物，可抑制肠道病毒 71 的复制和早期感染。
J Gen Virol. 2010 Nov;91(Pt 11):2734-44. doi: 10.1099/vir.0.023374-0. Epub 2010 Jul 21.
5
Cellular kinase inhibitors that suppress enterovirus replication have a conserved target in viral protein 3A similar to that of enviroxime.抑制肠道病毒复制的细胞激酶抑制剂在病毒蛋白3A中有一个与恩韦肟类似的保守靶点。
J Gen Virol. 2009 Aug;90(Pt 8):1869-1879. doi: 10.1099/vir.0.012096-0. Epub 2009 May 13.
6
Mutations in the nonstructural protein 3A confer resistance to the novel enterovirus replication inhibitor TTP-8307.非结构蛋白3A中的突变赋予了对新型肠道病毒复制抑制剂TTP-8307的抗性。
Antimicrob Agents Chemother. 2009 May;53(5):1850-7. doi: 10.1128/AAC.00934-08. Epub 2009 Feb 23.
7
Inflammatory rather than infectious insults play a role in exocrine tissue damage in a mouse model for coxsackievirus B4-induced pancreatitis.在柯萨奇病毒B4诱导的胰腺炎小鼠模型中，炎症而非感染性损伤在外分泌组织损伤中起作用。
J Pathol. 2009 Apr;217(5):633-41. doi: 10.1002/path.2501.
8
Increased gelatinase B/matrix metalloproteinase 9 (MMP-9) activity in a murine model of acute coxsackievirus B4-induced pancreatitis.在急性柯萨奇病毒B4诱导的小鼠胰腺炎模型中，明胶酶B/基质金属蛋白酶9（MMP-9）活性增加。
Virology. 2008 Dec 5;382(1):20-7. doi: 10.1016/j.virol.2008.08.046. Epub 2008 Oct 16.
9
Sequence determinants of 3A-mediated resistance to enviroxime in rhinoviruses and enteroviruses.鼻病毒和肠道病毒中3A介导的对环戊烯肟抗性的序列决定因素。
J Virol. 1996 Jul;70(7):4854-7. doi: 10.1128/JVI.70.7.4854-4857.1996.
10
The antiviral compound enviroxime targets the 3A coding region of rhinovirus and poliovirus.抗病毒化合物恩韦肟作用于鼻病毒和脊髓灰质炎病毒的3A编码区。
J Virol. 1995 Jul;69(7):4189-97. doi: 10.1128/JVI.69.7.4189-4197.1995.
Zotero 插件