Li Sai, Rissanen Ilona, Zeltina Antra, Hepojoki Jussi, Raghwani Jayna, Harlos Karl, Pybus Oliver G, Huiskonen Juha T, Bowden Thomas A
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Department of Virology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland.
Cell Rep. 2016 May 3;15(5):959-967. doi: 10.1016/j.celrep.2016.03.082. Epub 2016 Apr 21.
Hantaviruses, a geographically diverse group of zoonotic pathogens, initiate cell infection through the concerted action of Gn and Gc viral surface glycoproteins. Here, we describe the high-resolution crystal structure of the antigenic ectodomain of Gn from Puumala hantavirus (PUUV), a causative agent of hemorrhagic fever with renal syndrome. Fitting of PUUV Gn into an electron cryomicroscopy reconstruction of intact Gn-Gc spike complexes from the closely related but non-pathogenic Tula hantavirus localized Gn tetramers to the membrane-distal surface of the virion. The accuracy of the fitting was corroborated by epitope mapping and genetic analysis of available PUUV sequences. Interestingly, Gn exhibits greater non-synonymous sequence diversity than the less accessible Gc, supporting a role of the host humoral immune response in exerting selective pressure on the virus surface. The fold of PUUV Gn is likely to be widely conserved across hantaviruses.
汉坦病毒是一类地域分布广泛的人畜共患病原体，通过病毒表面糖蛋白Gn和Gc的协同作用引发细胞感染。在此，我们描述了普马拉汉坦病毒（PUUV）Gn抗原性胞外域的高分辨率晶体结构，PUUV是肾综合征出血热的病原体。将PUUV Gn拟合到来自密切相关但无致病性的图拉汉坦病毒完整Gn-Gc刺突复合物的电子冷冻显微镜重建中，将Gn四聚体定位到病毒粒子的膜远端表面。通过对可用PUUV序列的表位作图和遗传分析证实了拟合的准确性。有趣的是，Gn比难以接近的Gc表现出更大的非同义序列多样性，这支持宿主体液免疫反应在对病毒表面施加选择压力方面的作用。PUUV Gn的折叠可能在汉坦病毒中广泛保守。
