EMD-22646

Single-particle
4.2 Å
EMD-22646 Deposition: 09/09/2020
Map released: 23/09/2020
Last modified: 28/10/2020
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-22646

Murine polyomavirus with 8A7H5 Fab (icosahedral reconstruction)

EMD-22646

Single-particle
4.2 Å
EMD-22646 Deposition: 09/09/2020
Map released: 23/09/2020
Last modified: 28/10/2020
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Murine polyomavirus strain A2
Sample: Murine polyomavirus strain A2

Deposition Authors: Goetschius DJ, Hafenstein SL
Antibody escape by polyomavirus capsid mutation facilitates neurovirulence.
PUBMED: 32940605
DOI: doi:10.7554/eLife.61056
ISSN: 2050-084X
Abstract:
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.