Turnover rate of NS3 proteins modulates bluetongue virus replication kinetics in a host-specific manner

Najate Ftaich, Claire Ciancia, Cyril Viarouge, Gerald Barry, Maxime Ratinier, P.A. van Rijn, Emmanuel Breard, Damien Vitour, Stephan Zientara, Massimo Palmarini, Christophe Terzian, Frédérick Arnaud*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

Bluetongue virus (BTV) is an arbovirus transmitted to livestock by midges of the Culicoides family and is the etiological agent of a hemorrhagic disease in sheep and other ruminants. In mammalian cells, BTV particles are released primarily by virus-induced cell lysis, while in insect cells they bud from the plasma membrane and establish a persistent infection. BTV possesses a ten-segmented double-stranded RNA genome, and NS3 proteins are encoded by segment 10 (Seg-10). The viral nonstructural protein 3 (NS3) plays a key role in mediating BTV egress as well as in impeding the in vitro synthesis of type I interferon in mammalian cells. In this study, we asked whether genetically distant NS3 proteins can alter BTV-host interactions. Using a reverse genetics approach, we showed that, depending on the NS3 considered, BTV replication kinetics varied in mammals but not in insects. In particular, one of the NS3 proteins analyzed harbored a proline at position 24 that leads to its rapid intracellular decay in ovine but not in Culicoides cells and to the attenuation of BTV virulence in a mouse model of disease. Overall, our data reveal that the genetic variability of Seg-10/NS3 differentially modulates BTV replication kinetics in a host-specific manner and highlight the role of the host-specific variation in NS3 protein turnover rate.

Original languageEnglish
Pages (from-to)10467-10481
Number of pages15
JournalJournal of Virology
Volume89
Issue number20
DOIs
Publication statusPublished - 2015

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    Ftaich, N., Ciancia, C., Viarouge, C., Barry, G., Ratinier, M., van Rijn, P. A., Breard, E., Vitour, D., Zientara, S., Palmarini, M., Terzian, C., & Arnaud, F. (2015). Turnover rate of NS3 proteins modulates bluetongue virus replication kinetics in a host-specific manner. Journal of Virology, 89(20), 10467-10481. https://doi.org/10.1128/JVI.01541-15