Novel Toscana virus reverse genetics system establishes NSs as an antagonist of type I interferon responses

The sand fly-borne Toscana virus (TOSV) is the major cause of human meningoencephalitis in the Mediterranean basin during the summer season. In this work, we have developed a T7 RNA polymerase-driven reverse genetics system to recover infectious particles of a lineage B strain of TOSV. The viral pro...

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Main Authors: Wölfl, Franziska (Author) , Léger, Psylvia (Author) , Oreshkova, Nadia (Author) , Pahmeier, Felix (Author) , Windhaber, Stefan (Author) , Koch, Jana (Author) , Stanifer, Megan (Author) , Roman Sosa, Gleyder (Author) , Uckeley, Zina Maria (Author) , Rey, Felix A. (Author) , Boulant, Steeve (Author) , Kortekaas, Jeroen (Author) , Wichgers Schreur, Paul J. (Author) , Lozach, Pierre-Yves (Author)
Format: Article (Journal)
Language:English
Published: 4 April 2020
In: Viruses
Year: 2020, Volume: 12, Issue: 4
ISSN:1999-4915
DOI:10.3390/v12040400
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/v12040400
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1999-4915/12/4/400
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Author Notes:Franziska Woelfl, Psylvia Léger, Nadia Oreshkova, Felix Pahmeier, Stefan Windhaber, Jana Koch, Megan Stanifer, Gleyder Roman Sosa, Zina M. Uckeley, Felix A. Rey, Steeve Boulant, Jeroen Kortekaas, Paul J. Wichgers Schreur, and Pierre-Yves Lozach

MARC

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520 |a The sand fly-borne Toscana virus (TOSV) is the major cause of human meningoencephalitis in the Mediterranean basin during the summer season. In this work, we have developed a T7 RNA polymerase-driven reverse genetics system to recover infectious particles of a lineage B strain of TOSV. The viral protein pattern and growth properties of the rescued virus (rTOSV) were found to be similar to those of the corresponding wild-type (wt) virus. Using this system, we genetically engineered a TOSV mutant lacking expression of the non-structural protein NSs (rTOSVɸNSs). Unlike rTOSV and the wt virus, rTOSVɸNSs was unable to (i) suppress interferon (IFN)-b messenger RNA induction; and (ii) grow efficiently in cells producing IFN-b. Together, our results highlight the importance of NSs for TOSV in evading the IFN response and provide a comprehensive toolbox to investigate the TOSV life cycle in mammalian and insect host cells, including several novel polyclonal antibodies. 
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