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| タイトル | A broadly protective human antibody for GI genogroup noroviruses. |
|---|---|
| ジャーナル・号・ページ | Nat Microbiol, Vol. 10, Issue 5, Page 1227-1239, Year 2025 |
| 掲載日 | 2025年4月10日 |
著者 | Inga Rimkute / Adam S Olia / Mehin Suleiman / Kamron D Woods / Tatsiana Bylund / Nicholas C Morano / Ena S Tully / Raffaello Verardi / Saran Bao / Margaret H Beddall / Natthawan Chaimongkol / Mitzi M Donaldson / Renguang Du / Caitlyn N M Dulan / Jason Gorman / Amy R Henry / Chaim A Schramm / Stanislav V Sosnovtsev / Tyler Stephens / John-Paul Todd / Yaroslav Tsybovsky / Daniel C Douek / Kim Y Green / Reda Rawi / Lawrence Shapiro / Tongqing Zhou / Peter D Kwong / Mario Roederer / ![]() |
| PubMed 要旨 | Noroviruses infect millions each year, and while effective countermeasures are eagerly sought, none have been reported for the GI genogroup, first described more than 50 years ago. Here, to provide ...Noroviruses infect millions each year, and while effective countermeasures are eagerly sought, none have been reported for the GI genogroup, first described more than 50 years ago. Here, to provide insight into GI norovirus neutralization, we isolated a broad GI antibody, 16E10, from a human blood donor and showed it neutralizes noroviruses in human enteroid cultures and abrogates or reduces infection in rhesus macaques. The cryogenic electron microscopy reconstruction of 16E10 with a norovirus protruding-domain dimer at 2.56-Å resolution reveals an exceptionally large binding surface, overlapping an antibody supersite, distal from host receptor-binding or cofactor-binding sites. Cryogenic electron microscopy reconstructions with virus-like particles (VLPs) showed that 16E10 disrupts protruding domains on the VLP surface and disassembles VLPs, altering viral organization required for avidity. While its epitope was generally conserved, 16E10 recognized multiple sequence-divergent residues, binding to which was enabled by corresponding cavities in the 16E10-norovirus interface. Broad recognition of noroviruses can thus incorporate sequence-divergent residues, through a cavity-based mechanism of diversity tolerance. |
リンク | Nat Microbiol / PubMed:40211068 |
| 手法 | EM (単粒子) |
| 解像度 | 2.32 - 3.03 Å |
| 構造データ | ![]() EMDB-44672: GI.1 DS1 virus-like particle ![]() EMDB-44673: Norovirus GI.1 VLP bound to 16E10 Fab EMDB-44734, PDB-9bof: |
| 由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / norovirus / VP1 / P-domain / antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex |
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norovirus (ウイルス)
homo sapiens (ヒト)
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