Human Cytomegalovirus UL23 Attenuates Signal Transducer and Activator of Transcription 1 Phosphorylation and Type I Interferon Response.
Human Cytomegalovirus UL23 Attenuates Signal Transducer and Activator of Transcription 1 Phosphorylation and Type I Interferon Response.
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人类巨细胞病毒 UL23 减弱转录 1 磷酸化的信号转导器和激活剂以及 I 型干扰素反应
DOI：
10.3389/fmicb.2021.692515
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发表时间：
2021
影响因子：
5.2
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Feng L;Li W;Wu X;Li X;Yang X;Ran Y;Wu J;Li H
人巨细胞病毒（HCMV），人β-疱疹病毒，可导致严重的综合征，免疫功能低下的成年患者和新生儿。I型干扰素（IFN-Ⅰ）在抗病毒（如HCMV）感染中发挥重要作用，而IFN逃逸可能是病毒在宿主体内传播和疾病发生的关键决定因素。本研究证实，HCMV的被膜蛋白UL 23是负调节I型IFN免疫应答的关键因子。详细的分析表明，病毒UL 23蛋白在HCMV感染期间增加IFN-1抗病毒抗性。此外，UL 23显示出显著降低IFN-刺激的基因（ISG）的水平和IFN-1刺激的应答元件的启动子活性。在机制上，发现UL 23损害信号转导和转录激活因子1（STAT 1）磷酸化，尽管未发现其影响与IFN-1信号转导途径相关的STAT 2、Janus活化激酶1或酪氨酸激酶2的磷酸化和表达。此外，观察到STAT 1的核表达显著降低，但IFN调节因子9或STAT 2的核表达没有显著降低。本研究结果表明，HCMV UL 23是一种病毒拮抗剂，作用于细胞先天免疫，并揭示了UL 23对IFN-I信号转导的可能的新作用。
Human cytomegalovirus (HCMV), the human beta-herpesvirus, can cause severe syndromes among both immunocompromised adult patients and newborns. Type I interferon (IFN-I) exerts an important effect to resist infections caused by viruses such as HCMV, while IFN evasion may serve as a key determining factor for viral dissemination and disease occurrence within hosts. In this study, UL23, a tegument protein of HCMV, was confirmed to be a key factor for negatively regulating the type I IFN immune response. A detailed analysis indicated that the viral UL23 protein increases the IFN-I antiviral resistance during HCMV infections. Furthermore, UL23 was shown to significantly reduce the levels of IFN-stimulated genes (ISGs) and promoter activity of IFN-I-stimulated response element. Mechanically, UL23 was discovered to impair the signal transducer and activator of transcription 1 (STAT1) phosphorylation, although it was not found to affect phosphorylation and expression of STAT2, Janus activated kinase 1, or tyrosine kinase 2, which are associated with IFN-I signal transduction pathway. Additionally, a significantly reduced nuclear expression of STAT1 but not of IFN regulatory factor 9 or STAT2 was observed. Findings of this study indicate that HCMV UL23 is a viral antagonist that acts against the cellular innate immunity and reveal a possible novel effect of UL23 on IFN-I signaling.
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影响因子：
5.4
作者：
Cristea, Ileana M.;Moorman, Nathaniel J.;Shenk, Thomas
通讯作者：
Shenk, Thomas
影响因子：
6.7
作者：
Kim YE;Ahn JH
通讯作者：
Ahn JH
DOI：
10.3390/v10090447
发表时间：
2018-08-21
期刊：
Viruses
影响因子：
--
作者：
Goodwin CM;Ciesla JH;Munger J
通讯作者：
Munger J
影响因子：
56.9
作者：
Darnell, JE
通讯作者：
Darnell, JE
影响因子：
11.4
作者：
Cheon, HyeonJoo;Holvey-Bates, Elise G.;Schoggins, John W.;Forster, Samuel;Hertzog, Paul;Imanaka, Naoko;Rice, Charles M.;Jackson, Mark W.;Junk, Damian J.;Stark, George R.
通讯作者：
Stark, George R.