Heartland virus nss protein disrupts host defenses by blocking the tbk1 kinase-irf3 transcription factor interaction and signaling required for interferon induction
文献类型：期刊论文
| 作者 | Ning, Yun-Jia1; Feng, Kuan1,2; Min, Yuan-Qin1; Deng, Fei1; Hu, Zhihong1; Wang, Hualin1 |
| 刊名 | Journal of biological chemistry
 |
| 出版日期 | 2017-10-06 |
| 卷号 | 292期号:40页码:16722-16733 |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.m117.805127 |
| 通讯作者 | Wang, hualin(h.wang@wh.iov.cn) |
| 英文摘要 | Heartland virus (hrtv) is a pathogenic phlebovirus related to the severe fever with thrombocytopenia syndrome virus (sftsv), another phlebovirus causing life-threatening disease in humans. previous findings have suggested that sftsv can antagonize the host interferon (ifn) system via viral nonstructural protein (nss)-mediated sequestration of antiviral signaling proteins into nss-induced inclusion bodies. however, whether and how hrtv counteracts the host innate immunity is unknown. here, we report that hrtv nss (hnss) also antagonizes ifn and cytokine induction and bolsters viral replication, although no noticeable inclusion body formation was observed in hnss-expressing cells. furthermore, hnss inhibited the virus-triggered activation of ifn-beta promoter by specifically targeting the ifn-stimulated response element but not the nf-kappa b response element. consistently, hnss blocked the phosphorylation and nuclear translocation of ifn regulatory factor 3 (irf3, an ifn-stimulated response element-activating transcription factor). reporter gene assays next showed that hnss blockades the antiviral signaling mediated by rig-i-like receptors likely at the level of tank-binding kinase 1 (tbk1). indeed, hnss strongly interacts with tbk1 as indicated by confocal microscopy and pulldown analyses, and we also noted that the scaffold dimerization domain of tbk1 is required for the tbk1-hnss interaction. finally, pulldown assays demonstrated that hnss expression dose-dependently diminishes a tbk1-irf3 interaction, further explaining the mechanism for hnss function. collectively, these data suggest that hnss, an antagonist of host innate immunity, interacts with tbk1 and thereby hinders the association of tbk1 with its substrate irf3, thus blocking irf3 activation and transcriptional induction of the cellular antiviral responses. |
| WOS关键词 | THROMBOCYTOPENIA SYNDROME VIRUS ; NF-KAPPA-B ; I INTERFERON ; SEVERE FEVER ; RIG-I ; ADAPTER PROTEIN ; BUNYAVIRIDAE PHLEBOVIRUS ; NONSTRUCTURAL PROTEIN ; ANTIVIRAL IMMUNITY ; INCLUSION-BODIES |
| WOS研究方向 | Biochemistry & Molecular Biology |
| WOS类目 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| WOS记录号 | WOS:000412414800031 |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2373393 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Wang, Hualin |
| 作者单位 | 1.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ning, Yun-Jia,Feng, Kuan,Min, Yuan-Qin,et al. Heartland virus nss protein disrupts host defenses by blocking the tbk1 kinase-irf3 transcription factor interaction and signaling required for interferon induction[J]. Journal of biological chemistry,2017,292(40):16722-16733. |
| APA | Ning, Yun-Jia,Feng, Kuan,Min, Yuan-Qin,Deng, Fei,Hu, Zhihong,&Wang, Hualin.(2017).Heartland virus nss protein disrupts host defenses by blocking the tbk1 kinase-irf3 transcription factor interaction and signaling required for interferon induction.Journal of biological chemistry,292(40),16722-16733. |
| MLA | Ning, Yun-Jia,et al."Heartland virus nss protein disrupts host defenses by blocking the tbk1 kinase-irf3 transcription factor interaction and signaling required for interferon induction".Journal of biological chemistry 292.40(2017):16722-16733. |
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来源：武汉病毒研究所
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