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-Structure paper
| タイトル | Structural basis for childhood antibody recognition of the human metapneumovirus fusion protein. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 17, Issue 1, Page 1267, Year 2025 |
| 掲載日 | 2025年12月27日 |
著者 | Ahmed Magdy Khalil / Behrouz Ghazi Esfahani / Rose J Miller / Jiachen Huang / Guillermina Kuan / Angel Balmaseda / Aubree Gordon / Jarrod J Mousa / ![]() |
| PubMed 要旨 | 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) ...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. |
リンク | Nat Commun / PubMed:41455691 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.61 - 6.57 Å |
| 構造データ | EMDB-70793, PDB-9os5: EMDB-71547, PDB-9pdx: EMDB-71548, PDB-9pdy: ![]() EMDB-72382: Human antibody Fab MPV499 bound to hMPV DsCav-ES2 |
| 化合物 | ![]() ChemComp-NAG: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | IMMUNE SYSTEM / ANTIVIRAL PROTEIN / hMPV / Human respiratory disease / cryoem / human metapneumovirus / VIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex |
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homo sapiens (ヒト)
human metapneumovirus (ウイルス)
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