7K23

Murine polyomavirus hexavalent capsomer with 8A7H5 Fab, subparticle reconstruction

This is a non-PDB format compatible entry.

Summary for 7K23

• Entry DOI: 10.2210/pdb7k23/pdb
• EMDB information: 22641
• Descriptor: 8A7H5 Fab light chain, 8A7H5 Fab heavy chain, Capsid protein VP1 (3 entities in total)
• Functional Keywords: polyomavirus, capsomer, vp1, fab, viral protein
• Biological source: Mus musculus polyomavirus 1 (MPyV); More
• Total number of polymer chains: 15
• Total formula weight: 338986.55

Authors

Goetschius, D.J.,Hafenstein, S.L. (deposition date: 2020-09-08, release date: 2020-10-07, Last modification date: 2024-10-23)

Primary citation

Lauver, M.D.,Goetschius, D.J.,Netherby-Winslow, C.S.,Ayers, K.N.,Jin, G.,Haas, D.G.,Frost, E.L.,Cho, S.H.,Bator, C.,Bywaters, S.M.,Christensen, N.D.,Hafenstein, S.L.,Lukacher, A.E.
Antibody escape by polyomavirus capsid mutation facilitates neurovirulence.
Elife, 9:-, 2020

PubMed 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.

PubMed: 32940605
DOI: 10.7554/eLife.61056

Experimental method

ELECTRON MICROSCOPY (3.3 Å)