Orthobunyavirus spike architecture and recognition by neutralizing antibodies
| Autor: | Jan Hellert, Martin Beer, Ahmed Haouz, Kerstin Wernike, Félix A. Rey, Sven Reiche, Pablo Guardado-Calvo, Emiliana Brocchi, Andrea Aebischer |
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| Přispěvatelé: | Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Diagnostic Virology (IVD), Friedrich-Loeffler-Institut (FLI), Cristallographie (Plateforme) - Crystallography (Platform), Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna 'Bruno Ubertini' (IZSLER), This research was performed as part of the Zoonoses Anticipation and Preparedness Initiative (ZAPI project, IMI Grant Agreement n°115760), with the assistance and financial support of IMI and the European Commission, and in kind contributions from EFPIA partners. F.A.R. also received funding by the Région Ile de France (Domaine d’intêret majeur Innovative technologies for life sciences, DIM 1HEALTH). Additional funding was provided by Institut Pasteur, the CNRS and the GIS IBiSA (Infrastructures en biologie santé et agronomie). J.H. received the Pasteur-Cantarini fellowship for 24 months, and was later supported by the DIM 1HEALTH grant., We thank Patrick England from the Molecular Biophysics facility and Fabrice Agou from the Chemogenomic and Biological Screening platform at Institut Pasteur and the staff of synchrotron beamlines PX1 and PX2 at SOLEIL (St. Aubin, France) and ID29 and ID30B at the ESRF (Grenoble, France) for help during data collection. We thank Xiaohong Shi and Richard M. Elliott from Glasgow, UK, for the BUNV Gc gene., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Orthobunyavirus General Physics and Astronomy MESH: Cricetinae 02 engineering and technology MESH: Amino Acid Sequence Crystallography X-Ray medicine.disease_cause Genome MESH: Mice Knockout MESH: Antibodies Monoclonal MESH: Antibodies Neutralizing Mice MESH: Protein Structure Tertiary Viral Envelope Proteins MESH: Chlorocebus aethiops Cricetinae Chlorocebus aethiops MESH: Animals Neutralizing antibody lcsh:Science Mice Knockout Multidisciplinary biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Antibodies Monoclonal Schmallenberg virus Ruminants 021001 nanoscience & nanotechnology 3. Good health MESH: Ruminants Female Antibody 0210 nano-technology Viral protein Science MESH: Glycoproteins MESH: Orthobunyavirus MESH: Vero Cells Article General Biochemistry Genetics and Molecular Biology Antigenic drift 03 medical and health sciences MESH: Viral Structures MESH: Mice Inbred C57BL medicine Animals Amino Acid Sequence Vero Cells MESH: Mice Viral Structures Glycoproteins General Chemistry biology.organism_classification MESH: Crystallography X-Ray Antibodies Neutralizing Virology MESH: Male Protein Structure Tertiary Mice Inbred C57BL 030104 developmental biology MESH: Viral Envelope Proteins biology.protein Vero cell lcsh:Q MESH: Female |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature Communications Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.879. ⟨10.1038/s41467-019-08832-8⟩ Nature Communications, 2019, 10 (1), pp.879. ⟨10.1038/s41467-019-08832-8⟩ 'Nature Communications ', vol: 10, pages: 879-1-879-14 (2019) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-08832-8⟩ |
| Popis: | Orthobunyaviruses (OBVs) form a distinct genus of arthropod-borne bunyaviruses that can cause severe disease upon zoonotic transmission to humans. Antigenic drift or genome segment re-assortment have in the past resulted in new pathogenic OBVs, making them potential candidates for causing emerging zoonoses in the future. Low-resolution electron cryo-tomography studies have shown that OBV particles feature prominent trimeric spikes, but their molecular organization remained unknown. Here we report X-ray crystallography studies of four different OBVs showing that the spikes are formed by an N-terminal extension of the fusion glycoprotein Gc. Using Schmallenberg virus, a recently emerged OBV, we also show that the projecting spike is the major target of the neutralizing antibody response, and provide X-ray structures in complex with two protecting antibodies. We further show that immunization of mice with the spike domains elicits virtually sterilizing immunity, providing fundamental knowledge essential in the preparation for potential newly emerging OBV zoonoses. Orthobunyaviruses (OBVs) cause severe disease in humans and farm animals, but the molecular basis for infection is not fully understood. Here, the authors present crystal structures of free and antibody-bound OBV envelope glycoproteins and show that their domains enable efficient immunization in a mouse model. |
| Databáze: | OpenAIRE |
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