LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3
LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3
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LYAR 通过靶向磷酸化干扰素调节因子 3 抑制 β 干扰素诱导
DOI：
10.1128/jvi.00769-19
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发表时间：
2019-08
影响因子：
5.4
通讯作者：
Zhou Hongbo
中科院分区：
文献类型：
--
作者：
Yan Cha;Liu Xiaokun;Cheng Tailang;Xiao Rong;Gao Qingxia;Ming Fan;Jin Meilin;Chen Huanchun;Zhou Hongbo
I型干扰素（IFN-1）在保护宿主免受病毒感染的抗病毒先天免疫应答中起关键作用。IFN-I的负调节因子不仅对于微调对病原体的抗病毒反应很重要，而且对于预防过度炎症也很重要。识别负调节因子并研究其在先天免疫应答中的调节作用将为控制病毒性和炎症性疾病带来新的策略。在这里，我们报告的第一次，细胞生长调节核仁蛋白LYAR作为宿主先天免疫反应的阻遏物的行为。我们证明LYAR通过抑制IFN调节因子3（IRF 3）的DNA结合能力来负调节IFN-β介导的免疫应答。我们的研究揭示了LYAR在促进不同病毒复制事件中的共同机制，并提高了我们对宿主先天免疫应答负调控的认识。摘要先天性免疫应答是宿主防御的关键，必须严格控制，但其负调控机制尚不完全清楚。细胞生长调节蛋白LYAR在我们以前的研究中被发现可以促进多种病毒的复制。在这里，我们报告LYAR作为先天免疫反应的负调节因子。我们发现在病毒感染过程中，LYAR的表达被β干扰素（IFN-β）诱导。进一步的研究表明，LYAR与磷酸化的IFN调节因子3（IRF 3）相互作用，阻碍IRF 3的DNA结合能力，从而抑制IFN-β和下游IFN刺激基因（ISG）的转录。此外，LYAR抑制核因子-κB（NF-κB）介导的促炎细胞因子表达。总之，我们的研究揭示了LYAR通过靶向磷酸化IRF 3调节IFN-β介导的先天免疫应答的机制，这不仅有助于我们更好地理解LYAR调节病毒复制的机制，而且揭示了LYAR在宿主先天免疫中的新作用。重要性I型干扰素（IFN-I）在保护宿主免受病毒感染的抗病毒先天免疫应答中起着关键作用。IFN-I的负调节因子不仅对于微调对病原体的抗病毒反应很重要，而且对于预防过度炎症也很重要。识别负调节因子并研究其在先天免疫应答中的调节作用将为控制病毒性和炎症性疾病带来新的策略。在这里，我们报告的第一次，细胞生长调节核仁蛋白LYAR作为宿主先天免疫反应的阻遏物的行为。我们证明LYAR通过抑制IFN调节因子3（IRF 3）的DNA结合能力来负调节IFN-β介导的免疫应答。我们的研究揭示了LYAR在促进不同病毒复制事件中的共同机制，并提高了我们对宿主先天免疫应答负调控的认识。
Type I interferon (IFN-I) plays a critical role in the antiviral innate immune responses that protect the host against virus infection. The negative regulators of IFN-I are important not only for fine-tuning the antiviral responses to pathogens but also for preventing excessive inflammation. Identification of negative regulators and study of their modulation in innate immune responses will lead to new strategies for the control of both viral and inflammatory diseases. Here, we report for the first time that the cell growth-regulating nucleolar protein LYAR behaves as a repressor of host innate immune responses. We demonstrate that LYAR negatively regulates IFN-β-mediated immune responses by inhibiting the DNA binding ability of IFN regulatory factor 3 (IRF3). Our study reveals a common mechanism of LYAR in promoting different virus replication events and improves our knowledge of host negative regulation of innate immune responses. ABSTRACT The innate immune response is vital for host defense and must be tightly controlled, but the mechanisms responsible for its negative regulation are not fully understood. The cell growth-regulating nucleolar protein LYAR was found to promote replication of multiple viruses in our previous study. Here, we report that LYAR acts as a negative regulator of innate immune responses. We found that LYAR expression is induced by beta interferon (IFN-β) during virus infection. Further studies showed that LYAR interacts with phosphorylated IFN regulatory factor 3 (IRF3) to impede the DNA binding capacity of IRF3, thereby suppressing the transcription of IFN-β and downstream IFN-stimulated genes (ISGs). In addition, LYAR inhibits nuclear factor-κB (NF-κB)-mediated expression of proinflammatory cytokines. In summary, our study reveals the mechanism of LYAR in modulating IFN-β-mediated innate immune responses by targeting phosphorylated IRF3, which not only helps us to better understand the mechanisms of LYAR-regulated virus replication but also uncovers a novel role of LYAR in host innate immunity. IMPORTANCE Type I interferon (IFN-I) plays a critical role in the antiviral innate immune responses that protect the host against virus infection. The negative regulators of IFN-I are important not only for fine-tuning the antiviral responses to pathogens but also for preventing excessive inflammation. Identification of negative regulators and study of their modulation in innate immune responses will lead to new strategies for the control of both viral and inflammatory diseases. Here, we report for the first time that the cell growth-regulating nucleolar protein LYAR behaves as a repressor of host innate immune responses. We demonstrate that LYAR negatively regulates IFN-β-mediated immune responses by inhibiting the DNA binding ability of IFN regulatory factor 3 (IRF3). Our study reveals a common mechanism of LYAR in promoting different virus replication events and improves our knowledge of host negative regulation of innate immune responses.
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DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1401136
发表时间：
2014-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Yang S;Deng P;Zhu Z;Zhu J;Wang G;Zhang L;Chen AF;Wang T;Sarkar SN;Billiar TR;Wang Q
通讯作者：
Wang Q
CD169介导的HIV对树突状细胞中质膜起伏的运输减弱了抗GP120的疗效，广泛中和抗体。
影响因子：
6.7
作者：
Akiyama H;Ramirez NG;Gudheti MV;Gummuluru S
通讯作者：
Gummuluru S
影响因子：
3.7
作者：
Cuadrado E;Booiman T;van Hamme JL;Jansen MH;van Dort KA;Vanderver A;Rice GI;Crow YJ;Kootstra NA;Kuijpers TW
通讯作者：
Kuijpers TW
干扰素刺激的基因及其抗病毒效应子功能。
影响因子：
5.9
作者：
Schoggins, John W.;Rice, Charles M.
通讯作者：
Rice, Charles M.