Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein.
Nat Commun
; 8(1): 1528, 2017 11 16.
Article
in En
| MEDLINE
| ID: mdl-29142300
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Viral Fusion Proteins
/
Immunoglobulins, Intravenous
/
Metapneumovirus
/
Antibodies, Neutralizing
/
Antibodies, Viral
Limits:
Animals
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2017
Document type:
Article
Affiliation country:
Estados Unidos