Hantaviruses are rodent-borne viruses causing serious zoonotic outbreaks worldwide for which no treatment is available. X-ray structures of the hantavirus surface glycoprotein lattice reveal a built-in mechanism controlling envelope glycoprotein membrane insertion. This study provides important information for development of immunogen protection against these deadly viruses.
Rodent-borne hantaviruses form a close group of viruses distributed worldwide, classified as Old-World Hantaviruses and New World Hantaviruses (OWHs and NWHs, respectively) based on their geographical distribution and natural reservoirs (Jonsson et al., 2010: A Global Perspective on Hantavirus Ecology, Epidemiology, and Disease ). They cause life-threatening zoonotic outbreaks of severe pulmonary disease (NWHs) and hemorrhagic fever with renal syndrome (OWHs). Despite the severity of these diseases, no efficient treatment is available. Inhalation of aerosols contaminated with infected rodent excreta is the major route of transmission, although person-to-person transmission of a pulmonary syndrome caused by Andes hantavirus (ANDV) has also been reported. NWHs therefore have the potential to adapt to human- to-human airborne transmission routes, increasing their epidemic potential.
Hantavirus particles are pleomorphic and display a characteristic square surface lattice. Their envelope glycoproteins Gn and Gc form heterodimers that further assemble 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.
In this study, Serris, A. et al have described the high-resolution X-ray structures of the heterodimer of Gc and the Gn head and of the homotetrameric Gn base. Docking them into an 11.4-Å -resolution cryoelectron tomography map of the hantavirus surface accounted for the complete extramembrane portion of the viral glycoprotein shell and allowed a detailed description of the surface organization of these pleomorphic virions. These results, which further revealed a built-in mechanism controlling Gc membrane insertion for fusion, pave the way for immunogen design to protect against pathogenic hantaviruses.