National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01NS088367
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01NS092662
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI107121
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
F32NS106730
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
F31NS083336
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
T32CA060395
米国
引用
ジャーナル: Elife / 年: 2020 タイトル: Antibody escape by polyomavirus capsid mutation facilitates neurovirulence. 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 / ...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 / 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.
#221 - 2018年5月 ヒトパピローマウイルスとワクチン (Human Papillomavirus and Vaccines) 類似性 (1)
#200 - 2016年8月 正二十面体型ウイルスの準対称性 (Quasisymmetry in Icosahedral Viruses) 類似性 (5)
-
集合体
登録構造単位
L1: 8A7H5 Fab light chain H1: 8A7H5 Fab heavy chain F1: Capsid protein VP1 L2: 8A7H5 Fab light chain H2: 8A7H5 Fab heavy chain F2: Capsid protein VP1 L3: 8A7H5 Fab light chain H3: 8A7H5 Fab heavy chain F3: Capsid protein VP1 L4: 8A7H5 Fab light chain H4: 8A7H5 Fab heavy chain F4: Capsid protein VP1 L5: 8A7H5 Fab light chain H5: 8A7H5 Fab heavy chain F5: Capsid protein VP1