High-Resolution Description of the Hantavirus Surface Glycoprotein Lattice and Its Membrane Fusion Control Mechanism

Abstract

Hantaviruses are rodent-borne viruses causing serious zoonotic outbreaks worldwide for which no treatment is available. The hantavirus particles are pleomorphic and display a characteristic square surface lattice. The envelope glycoproteins Gn and Gc form heterodimeric protomers associated into tetrameric spikes, the lattice building blocks. The glycoproteins, which are the sole targets of neutralizing antibodies, drive virus entry via receptor-mediated endocytosis and endosomal membrane fusion. Here we describe the high-resolution X-ray structures of the Gn head / Gc heterodimer, and of the homotetrameric Gn base. Docking them into an 11.4 A resolution cryo- electron tomography map of the hantavirus surface accounted for the complete extracellular portion of the viral glycoprotein shell and provided unprecedented detail of the surface organization of a pleomorphic virus. These results, which further revealed an in-built mechanism controlling Gc membrane-insertion for fusion, pave the way for immunogen design to protect against pathogenic hantaviruses