A Molecular-Level Account of the Antigenic Hantaviral Surface.
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.
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Sai
S
Li
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Ilona
I
Rissanen
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Antra
A
Zeltina
Department of Virology, Haartman Institute, University of Helsinki, 00014 Helsinki, Finland.
Jussi
J
Hepojoki
Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
Jayna
J
Raghwani
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Karl
K
Harlos
Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK.
Oliver G
OG
Pybus
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. Electronic address: juha.huiskonen@strubi.ox.ac.uk.
Juha T
JT
Huiskonen
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. Electronic address: thomas.bowden@strubi.ox.ac.uk.
Thomas A
TA
Bowden
D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000276:immunology; D006023:Glycoproteins / Q000737:chemistry / Q000648:ultrastructure; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D011134:Polysaccharides / Q000737:chemistry; D000072417:Protein Domains; D029262:Puumala virus / Q000276:immunology*; D013499:Surface Properties; D014764:Viral Proteins / Q000737:chemistry / Q000648:ultrastructure; D014771:Virion / Q000648:ultrastructure
D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D011134:Polysaccharides; D014764:Viral Proteins