2026-06-14T03:30:35Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/71812024-09-27T20:00:26Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Battles, Michael B author Mas-Lloret, Vicente author Olmedillas Cela, Eduardo author Cano, Olga author Vazquez-Alcaraz, Monica author Rodriguez, Laura author Melero, Jose Antonio author McLellan, Jason S author 2017-11-16 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. Nat Commun. 2017 Nov 16;8(1):1528. 10.1038/s41467-017-01708-9 2041-1723 Nature communications 29142300 http://hdl.handle.net/20.500.12105/7181 Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein