Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments

Barski, M., Brennan, B. , Miller, O. K., Potter, J. A., Vijayakrishnan, S. , Bhella, D. , Naismith, J. H., Elliott, R. M. and Schwarz-Linek, U. (2017) Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments. eLife, 6, e29236. (doi:10.7554/elife.29236) (PMID:28915104) (PMCID:PMC5601994)

Barski, M., Brennan, B. , Miller, O. K., Potter, J. A., Vijayakrishnan, S. , Bhella, D. , Naismith, J. H., Elliott, R. M. and Schwarz-Linek, U. (2017) Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments. eLife, 6, e29236. (doi:10.7554/elife.29236) (PMID:28915104) (PMCID:PMC5601994)

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Abstract

Rift Valley fever phlebovirus (RVFV) is a clinically and economically important pathogen increasingly likely to cause widespread epidemics. RVFV virulence depends on the interferon antagonist non-structural protein (NSs), which remains poorly characterized. We identified a stable core domain of RVFV NSs (residues 83–248), and solved its crystal structure, a novel all-helical fold organized into highly ordered fibrils. A hallmark of RVFV pathology is NSs filament formation in infected cell nuclei. Recombinant virus encoding the NSs core domain induced intranuclear filaments, suggesting it contains all essential determinants for nuclear translocation and filament formation. Mutations of key crystal fibril interface residues in viruses encoding full-length NSs completely abrogated intranuclear filament formation in infected cells. We propose the fibrillar arrangement of the NSs core domain in crystals reveals the molecular basis of assembly of this key virulence factor in cell nuclei. Our findings have important implications for fundamental understanding of RVFV virulence.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Elliott, Professor Richard and Brennan, Dr Benjamin and Bhella, Professor David and Vijayakrishnan, Dr Swetha
Authors: Barski, M., Brennan, B., Miller, O. K., Potter, J. A., Vijayakrishnan, S., Bhella, D., Naismith, J. H., Elliott, R. M., and Schwarz-Linek, U.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:eLife
Publisher:eLife Sciences Publications, Ltd
ISSN:2050-084X
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2017 Barski et al.
First Published:First published in eLife 6: e29236
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
635361Molecular analyses of arbovirus-host interactionsMassimo PalmariniWellcome Trust (WELLCOTR)099220/B/12/ZMVLS III - CENTRE FOR VIRUS RESEARCH