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 |
| Creator Roles: | Elliott, R.Conceptualization, Funding acquisition, Supervision Brennan, B.Investigation, Resources, Visualization, Writing – review and editing Vijayakrishnan, S.Investigation, Visualization, Writing – review and editing Bhella, D.Resources, Supervision |
| 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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| 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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