Publication: Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein
Loading...
Identifiers
Publication date
2017-11-16
Authors
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
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group
Metrics
Export
Abstract
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.
Description
Keywords
MeSH Terms
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
DeCS Terms
Bibliographic citation
Nat Commun. 2017 Nov 16;8(1):1528.