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Structure paper

TitleStructural basis for childhood antibody recognition of the human metapneumovirus fusion protein.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Page 1267, Year 2025
Publish dateDec 27, 2025
AuthorsAhmed Magdy Khalil / Behrouz Ghazi Esfahani / Rose J Miller / Jiachen Huang / Guillermina Kuan / Angel Balmaseda / Aubree Gordon / Jarrod J Mousa /
PubMed AbstractHuman metapneumovirus (hMPV) is a significant cause of acute respiratory illness in children and older adults, with most children becoming seropositive by five years of age. The hMPV fusion (F) ...Human metapneumovirus (hMPV) is a significant cause of acute respiratory illness in children and older adults, with most children becoming seropositive by five years of age. The hMPV fusion (F) protein is the sole target of neutralizing antibodies, and while most common B-cell-targeted neutralizing epitopes on the hMPV F protein have been determined in hMPV-infected adults, the antibody response in hMPV-infected children remains undefined. We isolate five human monoclonal antibodies (mAbs) from hMPV-infected children, and evaluate their binding avidity, neutralization potency, epitope specificity, and in vivo efficacy. All mAbs are neutralizing, and epitope binning reveals four different epitopes targeted by the mAbs. Cryo-EM structures of four mAbs in complex with the hMPV F protein reveal epitopes on the hMPV F trimer surface as well as an intratrimer epitope located completely within the hMPV F trimer interface. Furthermore, we determine the prophylactic efficacy of the mAbs in protection against hMPV challenge in mice. These findings provide new insights into the immunodominant antigenic epitopes on the hMPV F protein in children and identify new mAbs for hMPV F disease prevention.
External linksNat Commun / PubMed:41455691 / PubMed Central
MethodsEM (single particle)
Resolution2.61 - 6.57 Å
Structure data

EMDB-70793, PDB-9os5:
Human antibody Fab MPV498 bound to hMPV B2 post-fusion F
Method: EM (single particle) / Resolution: 2.61 Å

EMDB-71547, PDB-9pdx:
Human antibody Fab MPV513 bound to hMPV DsCav-ES2
Method: EM (single particle) / Resolution: 3.94 Å

EMDB-71548, PDB-9pdy:
Human antibody Fab MPV510 bound to hMPV DsCav-ES2-IPDS F protein
Method: EM (single particle) / Resolution: 2.85 Å

EMDB-72382: Human antibody Fab MPV499 bound to hMPV DsCav-ES2
Method: EM (single particle) / Resolution: 6.57 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • human metapneumovirus
KeywordsIMMUNE SYSTEM / ANTIVIRAL PROTEIN / hMPV / Human respiratory disease / cryoem / human metapneumovirus / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex

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