近日,法国巴斯德研究所Pablo Guardado-Calvo、Felix A. Rey等研究人员合作揭示汉坦病毒表面糖蛋白晶格及其融合控制机制。这一研究成果于2020年9月15日在线发表在《细胞》上。
研究人员表示,汉坦病毒是啮齿动物传播的病毒,在世界范围内引起严重的人畜共患病爆发,目前尚无治疗方法。汉坦病毒颗粒是多形的,并显示出特征性的方形表面晶格。包膜糖蛋白Gn和Gc形成异二聚体,这些异二聚体进一步组装成四聚体峰,即晶格结构单元。糖蛋白是中和抗体的唯一靶标,它通过受体介导的内吞作用和内吞体膜融合来驱动病毒进入。
Title: The Hantavirus Surface Glycoprotein Lattice and Its Fusion Control Mechanism
Author: Alexandra Serris, Robert Stass, Eduardo A. Bignon, Nicolás A. Muena, Jean-Claude Manuguerra, Rohit K. Jangra, Sai Li, Kartik Chandran, Nicole D. Tischler, Juha T. Huiskonen, Felix A. Rey, Pablo Guardado-Calvo
Issue&Volume: 2020-09-15
Abstract: Hantaviruses are rodent-borne viruses causing serious zoonotic outbreaks worldwidefor which no treatment is available. Hantavirus particles are pleomorphic and displaya characteristic square surface lattice. The envelope glycoproteins Gn and Gc formheterodimers that further assemble into tetrameric spikes, the lattice building blocks.The glycoproteins, which are the sole targets of neutralizing antibodies, drive virusentry via receptor-mediated endocytosis and endosomal membrane fusion. Here we describethe high-resolution X-ray structures of the heterodimer of Gc and the Gn head andof the homotetrameric Gn base. Docking them into an 11.4--resolution cryoelectrontomography map of the hantavirus surface accounted for the complete extramembraneportion of the viral glycoprotein shell and allowed a detailed description of thesurface organization of these pleomorphic virions. Our results, which further revealeda built-in mechanism controlling Gc membrane insertion for fusion, pave the way forimmunogen design to protect against pathogenic hantaviruses.
DOI: 10.1016/j.cell.2020.08.023
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31064-3