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Merck
  • Antibody escape by polyomavirus capsid mutation facilitates neurovirulence.

Antibody escape by polyomavirus capsid mutation facilitates neurovirulence.

eLife (2020-09-18)
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
摘要

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.

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Millipore
Benzonase®核酸酶, ≥250 units/μL, ≥90% (SDS-PAGE), recombinant, expressed in E. coli, buffered aqueous glycerol solution
Sigma-Aldrich
神经氨酸酶 来源于霍乱弧菌, Type II, buffered aqueous solution, 8-24 units/mg protein (Lowry, using NAN-lactose)