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

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...

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Bibliographic Details
Published in:eLife 2017-09, Vol.6
Main Authors: Barski, Michal, Brennan, Benjamin, Miller, Ona K, Potter, Jane A, Vijayakrishnan, Swetha, Bhella, David, Naismith, James H, Elliott, Richard M, Schwarz-Linek, Ulrich
Format: Article
Language:English
Subjects:
Abortion
Active Transport, Cell Nucleus
Animal vaccines
Animals
Cell cycle
Cell Line
Cell Nucleus - virology
Coccidioidomycosis
Crystal structure
Crystallography, X-Ray
Crystals
DNA Mutational Analysis
Fibrils
Infections
Interferon
Kinases
Microbiology and Infectious Disease
Microscopy
Models, Molecular
Nuclear transport
Protein Conformation
Protein Multimerization
Protein structure
Proteins
Rift Valley fever
Rift valley fever virus
Rift Valley fever virus - chemistry
Rift Valley fever virus - genetics
RNA polymerase
Spectrum analysis
Structural Biology and Molecular Biophysics
Viral Nonstructural Proteins - chemistry
Viral Nonstructural Proteins - genetics
virulence factor
Virulence factors
Virulence Factors - chemistry
Virulence Factors - genetics
Viruses
X-ray crystallography
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.29236