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

DOI: 10.7554/eLife.29236 DOI Help

Authors: Michal Barski (University of St Andrews) , Benjamin Brennan (MRC-University of Glasgow Centre for Virus Research) , Ona K. Miller (University of St Andrews) , Jane A. Potter (University of St Andrews) , Swetha Vijayakrishnan (MRC-University of Glasgow Centre for Virus Research) , David Bhella (MRC-University of Glasgow Centre for Virus Research) , James H. Naismith (University of St Andrews) , Richard M. Elliot (MRC-University of Glasgow Centre for Virus Research) , Ulrich Schwarz-linek (University of St Andrews)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife

State: Published (Approved)
Published: September 2017
Diamond Proposal Number(s): 10071

Open Access Open Access

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.

Subject Areas: Biology and Bio-materials, Medicine

Instruments: I03-Macromolecular Crystallography