title: Toscana virus NSs protein inhibits the induction of type I interferon by interacting with RIG-I.
abstract: Toscana virus (TOSV) is a phlebovirus, of the Bunyaviridae family, that is responsible for central nervous system (CNS) injury in humans. Previous data have shown that the TOSV NSs protein is a gamma interferon (IFN-β) antagonist when transiently overexpressed in mammalian cells, inhibiting IRF-3 induction (G. Gori Savellini, F. Weber, C. Terrosi, M. Habjan, B. Martorelli, and M. G. Cusi, J. Gen. Virol. 92:71-79, 2011). In this study, we investigated whether an upstream sensor, which has a role in the signaling cascade leading to the production of type I IFN, was involved. We found a significant decrease in RIG-I protein levels in cells overexpressing TOSV NSs, suggesting that the nonstructural protein interacts with RIG-I and targets it for proteasomal degradation. In fact, the MG-132 proteasome inhibitor was able to restore IFN-β promoter activation in cells expressing NSs, demonstrating the existence of an evasion mechanism based on inhibition of the RIG-I sensor. Furthermore, a C-terminal truncated NSs protein (ΔNSs), although able to interact with RIG-I, did not affect the RIG-I-mediated IFN-β promoter activation, suggesting that the NSs domains responsible for RIG-I-mediated signaling and interaction with RIG-I are mapped on different regions. These results contribute to identify a novel mechanism for bunyaviruses by which TOSV NSs counteracts the early IFN response.
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Gori-Savellini
authors.forename: Melissa
authors.initials: M
authors.lastname: Valentini
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cusi
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008969:Molecular Sequence Data; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D029301:Sandfly fever Naples virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; C437968:PLAAT4 protein, human; D018168:Receptors, Retinoic Acid; D017361:Viral Nonstructural Proteins
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