Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein
Copyright policy )Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein
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.
- University of Helsinki Finland
- University of Lyon System France
- French National Centre for Scientific Research France
- Uppsala University Sweden
- École Normale Supérieure de Lyon France
glycoprotein, PATHOGENESIS, Antibodies, Viral, Puumala virus, hantavirus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 2400 General Immunology and Microbiology, structural biology, Biology (General), [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 11832 Microbiology and virology, Microbiology and Infectious Disease, Arvicolinae, General Neuroscience, Q, R, 2800 General Neuroscience, neutralizing antibody, Antibodies, Monoclonal, General Medicine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, SIN-NOMBRE, 570, QH301-705.5, infectious disease, Science, 610, 10184 Institute of Veterinary Pathology, Genetics and Molecular Biology, MEMBRANE-FUSION, NEUTRALIZING ANTIBODIES, 1300 General Biochemistry, Genetics and Molecular Biology, virus declared, molecular biophysics, PUUMALA VIRUS, Animals, Humans, structure, General Immunology and Microbiology, microbiology, Immunology in the medical area, Antibodies, Neutralizing, NEPHROPATHIA-EPIDEMICA, Biomedicine, HEMORRHAGIC-FEVER, HEK293 Cells, Immunologi inom det medicinska området, General Biochemistry, 570 Life sciences; biology, VIRUS ENVELOPE GLYCOPROTEINS, MONOCLONAL-ANTIBODIES, viral fusion, Viral Fusion Proteins, SYSTEM
glycoprotein, PATHOGENESIS, Antibodies, Viral, Puumala virus, hantavirus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 2400 General Immunology and Microbiology, structural biology, Biology (General), [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 11832 Microbiology and virology, Microbiology and Infectious Disease, Arvicolinae, General Neuroscience, Q, R, 2800 General Neuroscience, neutralizing antibody, Antibodies, Monoclonal, General Medicine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, SIN-NOMBRE, 570, QH301-705.5, infectious disease, Science, 610, 10184 Institute of Veterinary Pathology, Genetics and Molecular Biology, MEMBRANE-FUSION, NEUTRALIZING ANTIBODIES, 1300 General Biochemistry, Genetics and Molecular Biology, virus declared, molecular biophysics, PUUMALA VIRUS, Animals, Humans, structure, General Immunology and Microbiology, microbiology, Immunology in the medical area, Antibodies, Neutralizing, NEPHROPATHIA-EPIDEMICA, Biomedicine, HEMORRHAGIC-FEVER, HEK293 Cells, Immunologi inom det medicinska området, General Biochemistry, 570 Life sciences; biology, VIRUS ENVELOPE GLYCOPROTEINS, MONOCLONAL-ANTIBODIES, viral fusion, Viral Fusion Proteins, SYSTEM
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