NSs protein of Schmallenberg virus counteracts the antiviral response of the cell by inhibiting its transcriptional machinery.

Gerald Barry,Alain Kohl,Wolfgang Baumgärtner,Kerstin Hahn,Marco Caporale,Esther Schnettler,Massimo Palmarini,Maxime Ratinier,Mariana Varela,Frauke Seehusen,Anne-Lie Blomström

doi:10.1099/vir.0.065425-0

Abstract

Bunyaviruses have evolved a variety of strategies to counteract the antiviral defence systems of mammalian cells. Here we show that the NSs protein of Schmallenberg virus (SBV) induces the degradation of the RPB1 subunit of RNA polymerase II and consequently inhibits global cellular protein synthesis and the antiviral response. In addition, we show that the SBV NSs protein enhances apoptosis in vitro and possibly in vivo, suggesting that this protein could be involved in SBV pathogenesis in different ways.

Highlights

NSs protein of Schmallenberg virus counteracts the antiviral response of the cell by inhibiting its transcriptional machinery
We show that the Schmallenberg virus (SBV) NSs protein enhances apoptosis in vitro and possibly in vivo, suggesting that this protein could be involved in SBV pathogenesis in different ways
We previously showed that WT SBV and a NSs deletion mutant (SBVDNSs) do not differ in multiplication kinetics in a sheep cell line lacking a fully functional IFN system (CPT-Tert) (Arnaud et al, 2010; Varela et al, 2013)

Summary

Short Communication

To test if SBV could block host-cell gene and protein expression by suppressing transcription, translation or both (which would inhibit a strong antiviral response), we first infected HEK-293T cells with WT SBV or SBVDNSs at an m.o.i. of 1 and monitored nascent protein synthesis by 35S-methionine (PerkinElmer) labelling (0.8 MBq ml). Protein synthesis was decreased in both WT SBV- and SBVDNSs-infected cells, this effect appeared less pronounced in the latter (Fig. 1d) suggesting that NSs contributes to the inhibition of host-cell gene expression in SBV-infected cells. The virus protein bands at 16 h (bands ‘L’, ‘Gc’ and ‘N’ on the gel shown in Fig. 1d) were more prominent in SBVDNSsinfected cells The reasons for this are unclear, but it could suggest that NSs plays a regulatory/inhibitory role in the expression of other SBV proteins.

Tubulin T NSs

Mock Act D SBV Mock Act D SBV

Findings

SBV N protein