Structural highlights
Publication Abstract from PubMed
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 A 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.
Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein.,Battles MB, Mas V, Olmedillas E, Cano O, Vazquez M, Rodriguez L, Melero JA, McLellan JS Nat Commun. 2017 Nov 16;8(1):1528. doi: 10.1038/s41467-017-01708-9. PMID:29142300[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Battles MB, Mas V, Olmedillas E, Cano O, Vazquez M, Rodriguez L, Melero JA, McLellan JS. Structure and immunogenicity of pre-fusion-stabilized human metapneumovirus F glycoprotein. Nat Commun. 2017 Nov 16;8(1):1528. doi: 10.1038/s41467-017-01708-9. PMID:29142300 doi:http://dx.doi.org/10.1038/s41467-017-01708-9
