+検索条件
-Structure paper
タイトル | Antibody escape by polyomavirus capsid mutation facilitates neurovirulence. |
---|---|
ジャーナル・号・ページ | Elife, Vol. 9, Year 2020 |
掲載日 | 2020年9月17日 |
著者 | Matthew D Lauver / Daniel J Goetschius / Colleen S Netherby-Winslow / Katelyn N Ayers / Ge Jin / Daniel G Haas / Elizabeth L Frost / Sung Hyun Cho / Carol M Bator / Stephanie M Bywaters / Neil D Christensen / Susan L Hafenstein / Aron E Lukacher / |
PubMed 要旨 | JCPyV polyomavirus, a member of the human virome, causes progressive multifocal leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. ...JCPyV polyomavirus, a member of the human virome, causes progressive multifocal leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb) in vivo is unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo-EM and a custom sub-particle refinement approach, we resolved an MuPyV:Fab complex map to 3.2 Å resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation. |
リンク | Elife / PubMed:32940605 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 4.2 Å |
構造データ | EMDB-22640, PDB-7k22: EMDB-22641, PDB-7k23: EMDB-22642, PDB-7k24: EMDB-22643, PDB-7k25: EMDB-22645: EMDB-22646: |
由来 |
|
キーワード | VIRAL PROTEIN / polyomavirus / capsomer / VP1 / Fab |