The cellular chaperone heat shock protein 90 is required for foot-and-mouth disease virus capsid precursor processing and assembly of capsid pentamers

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Title: The cellular chaperone heat shock protein 90 is required for foot-and-mouth disease virus capsid precursor processing and assembly of capsid pentamers
Author(s): Newman, J
Asfor, AS
Berryman, S
Jackson, T
Curry, S
Tuthill, TJ
Item Type: Journal Article
Abstract: Productive picornavirus infection requires the hijack of host cell pathways to aid with the different stages of virus entry, synthesis of the viral polyprotein and viral genome replication. Many picornaviruses, including foot-and-mouth disease virus (FMDV), assemble capsids via the multimerisation of several copies of a single capsid precursor protein into a pentameric subunit which further encapsidates the RNA. Pentamer formation is preceded by co- and post-translational modification of the capsid precursor (P1-2A) by viral and cellular enzymes, and the subsequent rearrangement of P1-2A into a structure amenable to pentamer formation. We have developed a cell-free system to study FMDV pentamer assembly using recombinantly expressed FMDV capsid precursor and 3C protease. Using this assay, we have shown that two structurally different inhibitors of the cellular chaperone heat shock protein 90 (hsp90), impeded FMDV capsid precursor processing and subsequent pentamer formation. Treatment of FMDV permissive cells with the hsp90 inhibitor prior to infection reduced the endpoint titre by more than ten-fold while not affecting the activity of a sub-genomic replicon indicating that translation and replication of viral RNA were unaffected by the drug.
Publication Date: 6-Dec-2017
Date of Acceptance: 6-Dec-2017
URI: http://hdl.handle.net/10044/1/55758
DOI: https://dx.doi.org/10.1128/JVI.01415-17
ISSN: 1098-5514
Publisher: American Society for Microbiology
Journal / Book Title: Journal of Virology
Volume: 92
Issue: 5
Copyright Statement: Copyright © 2017 Newman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Keywords: Science & Technology
Life Sciences & Biomedicine
Virology
foot-and-mouth disease virus
hsp90
picornavirus
polyprotein processing
virus assembly
HSP90 MOLECULAR CHAPERONE
POLIOVIRUS P1 PRECURSOR
EMPTY CAPSIDS
3C PROTEASE
3-DIMENSIONAL STRUCTURE
SUBVIRAL PARTICLES
VIRAL REPLICATION
MAMMALIAN-CELLS
VP1/2A JUNCTION
INFECTED-CELLS
06 Biological Sciences
07 Agricultural And Veterinary Sciences
11 Medical And Health Sciences
Virology
Publication Status: Published
Article Number: e01415-17
Appears in Collections:Faculty of Natural Sciences



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