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-Structure paper
| タイトル | Molecular basis for shifted receptor recognition by an encephalitic arbovirus. |
|---|---|
| ジャーナル・号・ページ | Cell, Vol. 188, Issue 11, Page 2957-2973.e28, Year 2025 |
| 掲載日 | 2025年5月29日 |
著者 | Xiaoyi Fan / Wanyu Li / Jessica Oros / Jessica A Plante / Brooke M Mitchell / Jesse S Plung / Himanish Basu / Sivapratha Nagappan-Chettiar / Joshua M Boeckers / Laurentia V Tjang / Colin J Mann / Vesna Brusic / Tierra K Buck / Haley Varnum / Pan Yang / Linzy M Malcolm / So Yoen Choi / William M de Souza / Isaac M Chiu / Hisashi Umemori / Scott C Weaver / Kenneth S Plante / Jonathan Abraham / ![]() |
| PubMed 要旨 | Western equine encephalitis virus (WEEV) is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas. WEEV binds protocadherin 10 (PCDH10) as a receptor, and ...Western equine encephalitis virus (WEEV) is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas. WEEV binds protocadherin 10 (PCDH10) as a receptor, and highly virulent ancestral WEEV strains also bind low-density lipoprotein receptor (LDLR)-related proteins. As WEEV declined as a human pathogen in North America over the past century, isolates have lost the ability to bind mammalian receptors while still recognizing avian receptors. To explain shifts in receptor dependencies and assess the risk of WEEV re-emergence, we determined cryoelectron microscopy structures of WEEV bound to human PCDH10, avian PCDH10, and human very-low-density lipoprotein receptor (VLDLR). We show that one to three E2 glycoprotein substitutions are sufficient for a nonpathogenic strain to regain the ability to bind mammalian receptors. A soluble VLDLR fragment protects mice from lethal challenge by a virulent ancestral WEEV strain. Because WEEV recently re-emerged in South America after decades of inactivity, our findings have important implications for outbreak preparedness. |
リンク | Cell / PubMed:40187345 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.8 - 3.4 Å |
| 構造データ | EMDB-47116, PDB-9dqv: EMDB-47117, PDB-9dqx: EMDB-47118, PDB-9dqy: EMDB-47119, PDB-9dqz: |
| 化合物 | ![]() ChemComp-NAG: ![]() ChemComp-CA: |
| 由来 |
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キーワード | VIRUS LIKE PARTICLE / western equine encephalitis virus / WEEV / receptor binding / PCDH10 / virus like particles / VLDLR |
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western equine encephalitis virus (西部ウマ脳炎ウイルス)
homo sapiens (ヒト)
passer domesticus (イエスズメ)
キーワード