Cytoplasmic Translocation of Nucleolar Protein NOP53 Promotes Viral Replication by Suppressing Host Defense.
Cytoplasmic Translocation of Nucleolar Protein NOP53 Promotes Viral Replication by Suppressing Host Defense.
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核仁蛋白 NOP53 的细胞质易位通过抑制宿主防御促进病毒复制
DOI：
10.3390/v10040208
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发表时间：
2018-04-20
期刊：
影响因子：
--
通讯作者：
Wang XJ
中科院分区：
文献类型：
--
作者：
Meng W;Han SC;Li CC;Dong HJ;Chang JY;Wang HR;Wang XJ
NOP 53是位于核仁中的肿瘤抑制蛋白，并且在水泡性口炎病毒（VSV）和单纯疱疹病毒1型（HSV-1）感染期间移位到细胞质，如我们先前的研究所示。细胞质N 0 P53与视黄酸诱导基因I（RIG-I）相互作用以去除其K63连接的泛素化，导致I型干扰素IFN-β的减弱。在本研究中，我们没有发现明显的易位的NOP 53感染的突变病毒缺乏ICP 4（HSV-1/d120，复制不足）。通过删除其核输出序列（内斯）阻断NOP 53的胞质易位，消除了其支持病毒复制的能力。这些结果表明，NOP 53再分布与病毒复制有关。有趣的是，用poly（I：C）或RIG-I-N（组成型活性变体）处理直接诱导NOP 53胞质易位。为了更好地评估细胞质NOP 53在病毒复制中的功能，构建并表达了NOP 53衍生的蛋白N3-T，其在N3的C-末端区域（残基330-432）含有人免疫缺陷病毒（HIV）衍生的细胞穿透达特肽。重组N3-T蛋白形成三聚体，减弱IFN-β和IFN刺激基因的表达，并降低干扰素调节因子3（IRF 3）的磷酸化水平。此外，N3-T促进了属于5个科的有包膜和无包膜DNA和RNA病毒的有效复制。我们的研究结果扩展了对病毒利用核仁蛋白NOP 53进行最佳病毒复制的机制的理解。
NOP53 is a tumor suppressor protein located in the nucleolus and is translocated to the cytoplasm during infection by vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1), as shown in our previous study. Cytoplasmic NOP53 interacts with the retinoic acid-inducible gene I (RIG-I) to remove its K63-linked ubiquitination, leading to attenuation of type I interferon IFN-β. In the present study, we found no obvious translocation of NOP53 in infection by a mutant virus lacking ICP4 (HSV-1/d120, replication inadequate). Blocking cytoplasmic translocation of NOP53 by the deletion of its nuclear export sequence (NES) abrogated its ability to support viral replication. These results demonstrated that NOP53 redistribution is related to viral replication. It is interesting that treatment with poly (I:C) or RIG-I-N (a constitutively-active variant) directly induced NOP53 cytoplasmic translocation. To better assess the function of cytoplasmic NOP53 in viral replication, the NOP53-derived protein N3-T, which contains a human immunodeficiency virus (HIV)-derived cell-penetrating Tat peptide at the C-terminal region of N3 (residues 330–432), was constructed and expressed. The recombinant N3-T protein formed trimers, attenuated the expression of IFN-β and IFN-stimulated genes, as well as decreased the phosphorylation level of interferon regulatory factor 3 (IRF3). Furthermore, N3-T promoted the efficient replication of enveloped and non-enveloped DNA and RNA viruses belonging to 5 families. Our findings expand the understanding of the mechanism by which viruses utilize the nucleolar protein NOP53 for optimal viral replication.
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