NP 蛋白的泛素化和去泛素化调节甲型流感病毒 RNA 的复制。
Ubiquitination and deubiquitination of NP protein regulates influenza A virus RNA replication.
机构信息
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
出版信息
EMBO J. 2010 Nov 17;29(22):3879-90. doi: 10.1038/emboj.2010.250. Epub 2010 Oct 5.
Abstract
Influenza A virus RNA replication requires an intricate regulatory network involving viral and cellular proteins. In this study, we examined the roles of cellular ubiquitinating/deubiquitinating enzymes (DUBs). We observed that downregulation of a cellular deubiquitinating enzyme USP11 resulted in enhanced virus production, suggesting that USP11 could inhibit influenza virus replication. Conversely, overexpression of USP11 specifically inhibited viral genomic RNA replication, and this inhibition required the deubiquitinase activity. Furthermore, we showed that USP11 interacted with PB2, PA, and NP of viral RNA replication complex, and that NP is a monoubiquitinated protein and can be deubiquitinated by USP11 in vivo. Finally, we identified K184 as the ubiquitination site on NP and this residue is crucial for virus RNA replication. We propose that ubiquitination/deubiquitination of NP can be manipulated for antiviral therapeutic purposes.
摘要
甲型流感病毒 RNA 复制需要一个涉及病毒和细胞蛋白的复杂调控网络。在这项研究中，我们研究了细胞泛素化/去泛素化酶（DUBs）的作用。我们发现，下调一种细胞去泛素化酶 USP11 会导致病毒产量增加，表明 USP11 可能抑制流感病毒复制。相反，USP11 的过表达特异性抑制病毒基因组 RNA 复制，这种抑制需要去泛素酶活性。此外，我们表明 USP11 与病毒 RNA 复制复合物的 PB2、PA 和 NP 相互作用，并且 NP 是一个单泛素化蛋白，可在体内被 USP11 去泛素化。最后，我们确定 NP 上的 K184 是泛素化位点，该残基对病毒 RNA 复制至关重要。我们提出可以操纵 NP 的泛素化/去泛素化来进行抗病毒治疗。
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本文引用的文献
1
Influenza A virus-generated small RNAs regulate the switch from transcription to replication.甲型流感病毒生成的小 RNA 调节转录到复制的转换。
Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11525-30. doi: 10.1073/pnas.1001984107. Epub 2010 Jun 1.
2
Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication.全基因组 RNAi 筛选鉴定出流感病毒复制所必需的人类宿主因子。
Nature. 2010 Feb 11;463(7282):818-22. doi: 10.1038/nature08760. Epub 2010 Jan 17.
3
Human host factors required for influenza virus replication.流感病毒复制所需的人体宿主因素。
Nature. 2010 Feb 11;463(7282):813-7. doi: 10.1038/nature08699.
4
A genome-wide genetic screen for host factors required for hepatitis C virus propagation.一项针对丙型肝炎病毒传播所需宿主因子的全基因组遗传筛选。
Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16410-5. doi: 10.1073/pnas.0907439106. Epub 2009 Aug 27.
5
A single substitution in amino acid 184 of the NP protein alters the replication and pathogenicity of H5N1 avian influenza viruses in chickens.核蛋白（NP）第184位氨基酸的单个替换改变了H5N1禽流感病毒在鸡体内的复制和致病性。
Arch Virol. 2009;154(6):969-79. doi: 10.1007/s00705-009-0399-4. Epub 2009 May 28.
6
Mutational analysis of conserved amino acids in the influenza A virus nucleoprotein.甲型流感病毒核蛋白中保守氨基酸的突变分析
J Virol. 2009 May;83(9):4153-62. doi: 10.1128/JVI.02642-08. Epub 2009 Feb 18.
7
Interaction of the influenza a virus nucleocapsid protein with the viral RNA polymerase potentiates unprimed viral RNA replication.甲型流感病毒核衣壳蛋白与病毒RNA聚合酶的相互作用增强了无引物的病毒RNA复制。
J Virol. 2009 Jan;83(1):29-36. doi: 10.1128/JVI.02293-07. Epub 2008 Oct 22.
8
RNA interference screen for human genes associated with West Nile virus infection.针对与西尼罗河病毒感染相关的人类基因的RNA干扰筛选。
Nature. 2008 Sep 11;455(7210):242-5. doi: 10.1038/nature07207.
9
Transcription of subgenomic mRNA of hepatitis delta virus requires a modified hepatitis delta antigen that is distinct from antigenomic RNA synthesis.丁型肝炎病毒亚基因组mRNA的转录需要一种不同于反基因组RNA合成的修饰丁型肝炎抗原。
J Virol. 2008 Oct;82(19):9409-16. doi: 10.1128/JVI.00428-08. Epub 2008 Jul 23.
10
Drosophila RNAi screen identifies host genes important for influenza virus replication.果蝇RNA干扰筛选鉴定出对流感病毒复制重要的宿主基因。
Nature. 2008 Aug 14;454(7206):890-3. doi: 10.1038/nature07151. Epub 2008 Jul 9.
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