Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/7181
Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein
Battles, Michael B | Mas-Lloret, Vicente ISCIII | Olmedillas Cela, Eduardo ISCIII | Cano, Olga ISCIII | Vazquez-Alcaraz, Monica ISCIII | Rodriguez, Laura ISCIII | Melero, Jose Antonio ISCIII | McLellan, Jason S
Nat Commun. 2017 Nov 16;8(1):1528.
Human metapneumovirus (hMPV) is a frequent cause of bronchiolitis in young children. Its F glycoprotein mediates virus-cell membrane fusion and is the primary target of neutralizing antibodies. The inability to produce recombinant hMPV F glycoprotein in the metastable pre-fusion conformation has hindered structural and immunological studies. Here, we engineer a pre-fusion-stabilized hMPV F ectodomain and determine its crystal structure to 2.6 Å resolution. This structure reveals molecular determinants of strain-dependent acid-induced fusion, as well as insights into refolding from pre- to post-fusion conformations. A dense glycan shield at the apex of pre-fusion hMPV F suggests that antibodies against this site may not be elicited by host immune responses, which is confirmed by depletion studies of human immunoglobulins and by mouse immunizations. This is a major difference with pre-fusion F from human respiratory syncytial virus (hRSV), and collectively our results should facilitate development of effective hMPV vaccine candidates.
Animals | Antibodies, Neutralizing | Antibodies, Viral | Cercopithecus aethiops | Crystallography, X-Ray | Female | Immunoglobulins, Intravenous | Metapneumovirus | Mice | Mice, Inbred BALB C | Protein Domains | Protein Engineering | Protein Refolding | Recombinant Proteins | Respiratory Syncytial Virus, Human | Vero Cells | Viral Fusion Proteins
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