7k25

Murine polyomavirus hexavalent capsomer, subparticle reconstruction

spinqualitylabelsall models 7k25, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 A 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. Antibody escape by polyomavirus capsid mutation facilitates neurovirulence.,Lauver MD, Goetschius DJ, Netherby-Winslow CS, Ayers KN, Jin G, Haas DG, Frost EL, Cho SH, Bator C, Bywaters SM, Christensen ND, Hafenstein SL, Lukacher AE Elife. 2020 Sep 17;9. pii: 61056. doi: 10.7554/eLife.61056. PMID:32940605 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus coat proteins 3D structures

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