Recent advances in bunyavirus glycoprotein research: precursor processing, receptor binding and structure

The Bunyavirales order accommodates related viruses (bunyaviruses) with segmented, linear, single-stranded, negative- or ambi-sense RNA genomes. Their glycoproteins form capsomeric projections or spikes on the virion surface and play a crucial role in virus entry, assembly, morphogenesis. Bunyavirus glycoproteins are encoded by a single RNA segment as a polyprotein precursor that is co- and post-translationally cleaved by host cell enzymes to yield two mature glycoproteins, Gn and Gc (or GP1 and GP2 in arenaviruses). These glycoproteins undergo extensive N-linked glycosylation and despite their cleavage, remain associated to the virion to form an integral transmembrane glycoprotein complex. This review summarizes recent advances in our understanding of the molecular biology of bunyavirus glycoproteins, including their processing, structure, and known interactions with host factors that facilitate cell entry

Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein

Rissanen, Ilona Stass, Robert Krumm, Stefanie A Seow, Jeffrey Hulswit, Ruben Jg Paesen, Guido C Hepojoki, Jussi Vapalahti, Olli Lundkvist, Ake Reynard, Olivier Volchkov, Viktor Doores, Katie J Huiskonen, Juha T Bowden, Thomas A eng MR/L009528/1/Medical Research Council/United Kingdom MR/S007555/1/Medical Research Council/United Kingdom MR/N002091/1/Medical Research Council/United Kingdom MR/K024426/1/Medical Research Council/United Kingdom 309605/Academy of Finland 649053/H2020 European Research Council 203141/Z/16Z/Wellcome Trust/United Kingdom 060208/Z/00/Z/Wellcome Trust/United Kingdom 093305/Z/10/Z/Wellcome Trust/United Kingdom England Elife. 2020 Dec 22;9. pii: 58242. doi: 10.7554/eLife.58242.The intricate lattice of Gn and Gc glycoprotein spike complexes on the hantavirus envelope facilitates host-cell entry and is the primary target of the neutralizing antibody-mediated immune response. Through study of a neutralizing monoclonal antibody termed mAb P-4G2, which neutralizes the zoonotic pathogen Puumala virus (PUUV), we provide a molecular-level basis for antibody-mediated targeting of the hantaviral glycoprotein lattice. Crystallographic analysis demonstrates that P-4G2 binds to a multi-domain site on PUUV Gc and may preclude fusogenic rearrangements of the glycoprotein that are required for host-cell entry. Furthermore, cryo-electron microscopy of PUUV-like particles in the presence of P-4G2 reveals a lattice-independent configuration of the Gc, demonstrating that P-4G2 perturbs the (Gn-Gc)4 lattice. This work provides a structure-based blueprint for rationalizing antibody-mediated targeting of hantaviruses.Peer reviewe