Battles, Michael BMas-Lloret, VicenteOlmedillas Cela, EduardoCano, OlgaVazquez-Alcaraz, MonicaRodriguez, LauraMelero, Jose AntonioMcLellan, Jason S2019-02-192019-02-192017-11-16Nat Commun. 2017 Nov 16;8(1):1528.2041-1723http://hdl.handle.net/20.500.12105/7181Human 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.engVoRhttp://creativecommons.org/licenses/by/4.0/AnimalsAntibodies, NeutralizingAntibodies, ViralCercopithecus aethiopsCrystallography, X-RayFemaleImmunoglobulins, IntravenousMetapneumovirusMiceMice, Inbred BALB CProtein DomainsProtein EngineeringProtein RefoldingRecombinant ProteinsRespiratory Syncytial Virus, HumanVero CellsViral Fusion ProteinsAtribución 4.0 Internacional2914230081152810.1038/s41467-017-01708-9Nature communicationsopen access