Nonstructural Protein NSs of Schmallenberg Virus Is Targeted to the Nucleolus and Induces Nucleolar Disorganization.
Nonstructural Protein NSs of Schmallenberg Virus Is Targeted to the Nucleolus and Induces Nucleolar Disorganization.
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DOI：
10.1128/jvi.01263-16
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发表时间：
2017-01-01
影响因子：
5.4
通讯作者：
Vitour D
中科院分区：
文献类型：
--
作者：
Gouzil J;Fablet A;Lara E;Caignard G;Cochet M;Kundlacz C;Palmarini M;Varela M;Breard E;Sailleau C;Viarouge C;Coulpier M;Zientara S;Vitour D
施马伦贝格病毒（SBV）于 2011 年底在德国发现，随后迅速传播到许多欧洲国家。 SBV 是一种正布尼亚病毒，可导致反刍动物流产和先天性畸形。病毒编码的非结构蛋白（称为 NSs）是 SBV 的主要毒力因子，已知它会促进 Rpb1（RNA 聚合酶 II (Pol II) 复合物的亚基）的降解，从而阻碍整体细胞转录。在这项研究中，我们发现 NS 主要定位于受感染细胞的细胞核中，并且似乎通过位于蛋白质残基 33 和 51 之间的核仁定位信号 (NoLS) 特异性地靶向核仁。 NS 与 B23（核磷蛋白）和原纤维蛋白等核仁标记物共定位。我们观察到，在 SBV 感染的细胞中，B23 经历核仁到核质的重新分配，这让人想起病毒诱导的核仁破坏。相比之下，B23 的核仁模式在用缺乏 NoLS 基序的 NS 的 SBV 重组突变体 (SBVΔNoLS) 感染后没有变化。有趣的是，与野生型 SBV 不同，SBVΔNoLS 对 RNA Pol II 转录的抑制活性受损。总体而言，我们的结果表明，NSs 诱导的核仁破坏与其对细胞转录的抑制功能之间存在假定的联系，从而阻止细胞抗病毒反应和/或诱导细胞死亡。重要性 施马伦贝格病毒 (SBV) 是一种新兴的反刍动物虫媒病毒，于 2011 年至 2013 年间在欧洲传播。SBV 会导致妊娠期间胎儿畸形，其中中枢神经系统是受影响最严重的器官之一。病毒编码的 NSs 蛋白通过损害宿主细胞转录充当毒力因子。在这里，我们发现 NSs 含有核仁定位信号（NoLS）并诱导核仁解体。 SBV NS 中的 NoLS 基序对于病毒诱导的细胞转录抑制是绝对必要的。据我们所知，这是布尼亚病毒科中 NS 的核仁功能的第一份报告。
Schmallenberg virus (SBV) was discovered in Germany in late 2011 and then spread rapidly to many European countries. SBV is an orthobunyavirus that causes abortion and congenital abnormalities in ruminants. A virus-encoded nonstructural protein, termed NSs, is a major virulence factor of SBV, and it is known to promote the degradation of Rpb1, a subunit of the RNA polymerase II (Pol II) complex, and therefore hampers global cellular transcription. In this study, we found that NSs is mainly localized in the nucleus of infected cells and specifically appears to target the nucleolus through a nucleolar localization signal (NoLS) localized between residues 33 and 51 of the protein. NSs colocalizes with nucleolar markers such as B23 (nucleophosmin) and fibrillarin. We observed that in SBV-infected cells, B23 undergoes a nucleolus-to-nucleoplasm redistribution, evocative of virus-induced nucleolar disruption. In contrast, the nucleolar pattern of B23 was unchanged upon infection with an SBV recombinant mutant with NSs lacking the NoLS motif (SBVΔNoLS). Interestingly, unlike wild-type SBV, the inhibitory activity of SBVΔNoLS toward RNA Pol II transcription is impaired. Overall, our results suggest that a putative link exists between NSs-induced nucleolar disruption and its inhibitory function on cellular transcription, which consequently precludes the cellular antiviral response and/or induces cell death. IMPORTANCE Schmallenberg virus (SBV) is an emerging arbovirus of ruminants that spread in Europe between 2011 and 2013. SBV induces fetal abnormalities during gestation, with the central nervous system being one of the most affected organs. The virus-encoded NSs protein acts as a virulence factor by impairing host cell transcription. Here, we show that NSs contains a nucleolar localization signal (NoLS) and induces disorganization of the nucleolus. The NoLS motif in the SBV NSs is absolutely necessary for virus-induced inhibition of cellular transcription. To our knowledge, this is the first report of nucleolar functions for NSs within the Bunyaviridae family.