Guo Yusong R, Hryc Corey F, Jakana Joanita, Jiang Hongbing, Wang David, Chiu Wah, Zhong Weiwei, Tao Yizhi J
Department of BioSciences, Rice University, Houston, TX 77005;
Graduate Program in Structural and Computational Biology and Molecular Biophysics and Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030; and.
Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12781-6. doi: 10.1073/pnas.1407122111. Epub 2014 Aug 18.
Orsay, the first virus discovered to naturally infect Caenorhabditis elegans or any nematode, has a bipartite, positive-sense RNA genome. Sequence analyses show that Orsay is related to nodaviruses, but molecular characterizations of Orsay reveal several unique features, such as the expression of a capsid-δ fusion protein and the use of an ATG-independent mechanism for translation initiation. Here we report the crystal structure of an Orsay virus-like particle assembled from recombinant capsid protein (CP). Orsay capsid has a T = 3 icosahedral symmetry with 60 trimeric surface spikes. Each CP can be divided into three regions: an N-terminal arm that forms an extended protein interaction network at the capsid interior, an S domain with a jelly-roll, β-barrel fold forming the continuous capsid, and a P domain that forms surface spike projections. The structure of the Orsay S domain is best aligned to T = 3 plant RNA viruses but exhibits substantial differences compared with the insect-infecting alphanodaviruses, which also lack the P domain in their CPs. The Orsay P domain is remotely related to the P1 domain in calicivirus and hepatitis E virus, suggesting a possible evolutionary relationship. Removing the N-terminal arm produced a slightly expanded capsid with fewer nucleic acids packaged, suggesting that the arm is important for capsid stability and genome packaging. Because C. elegans-Orsay serves as a highly tractable model for studying viral pathogenesis, our results should provide a valuable structural framework for further studies of Orsay replication and infection.
奥赛病毒是首个被发现能自然感染秀丽隐杆线虫或任何线虫的病毒，其基因组为双链正链RNA。序列分析表明，奥赛病毒与诺达病毒有关，但对奥赛病毒的分子特征分析揭示了几个独特特征，如衣壳-δ融合蛋白的表达以及使用不依赖ATG的翻译起始机制。在此，我们报告了由重组衣壳蛋白（CP）组装而成的奥赛病毒样颗粒的晶体结构。奥赛病毒衣壳具有T = 3的二十面体对称性，有60个三聚体表面刺突。每个CP可分为三个区域：在衣壳内部形成扩展蛋白相互作用网络的N端臂、具有果冻卷β桶折叠形成连续衣壳的S结构域以及形成表面刺突突起的P结构域。奥赛病毒S结构域的结构与T = 3植物RNA病毒最匹配，但与感染昆虫的α诺达病毒相比存在显著差异，后者的CP中也缺乏P结构域。奥赛病毒P结构域与杯状病毒和戊型肝炎病毒中的P1结构域有远缘关系，提示可能存在进化关系。去除N端臂会使衣壳略有扩张，包装的核酸减少，这表明该臂对衣壳稳定性和基因组包装很重要。由于秀丽隐杆线虫-奥赛病毒是研究病毒发病机制的高度易处理模型，我们的结果应为进一步研究奥赛病毒的复制和感染提供有价值的结构框架。
