Journalartikel

Jahr der Veröffentlichung: 2018

Zeitschrift: Journal of Virology

Bandnummer: 92

Heftnummer: 23

ISSN: 0022-538X

eISSN: 1098-5514

Open Access Status: Hybrid

DOI Link: https://doi.org/10.1128/JVI.01202-18

Verlag: American Society for Microbiology

Abstract: 

Sandfly fever Sicilian virus (SFSV) is one of the most widespread and frequently identified members of the genus Phlebovirus (order Bunyavirales, family Phenuiviridae) infecting humans. Being transmitted by Phlebotomus sandflies, SFSV causes a self-limiting, acute, often incapacitating febrile disease (“sandfly fever,” “Pappataci fever,” or “dog disease”) that has been known since at least the beginning of the 20th century. We show that, similarly to other pathogenic phleboviruses, SFSV suppresses the induction of the antiviral type I interferon (IFN) system in an NSs-dependent manner. SFSV NSs interfered with the TBK1-interferon regulatory factor 3 (IRF3) branch of the RIG-I signaling pathway but not with NF-κB activation. Consistently, we identified IRF3 as a host interactor of SFSV NSs. In contrast to IRF3, neither the IFN master regulator IRF7 nor any of the related transcription factors IRF2, IRF5, and IRF9 were bound by SFSV NSs. In spite of this specificity for IRF3, NSs did not inhibit its phosphorylation, dimerization, or nuclear accumulation, and the interaction was independent of the IRF3 activation or multimerization state. In further studies, we identified the DNA-binding domain of IRF3 (amino acids 1 to 113) as sufficient for NSs binding and found that SFSV NSs prevented the association of activated IRF3 with the IFN-β promoter. Thus, unlike highly virulent phleboviruses, which either destroy antiviral host factors or sequester whole signaling chains into inactive aggregates, SFSV modulates type I IFN induction by directly masking the DNA-binding domain of IRF3.

Harvard-Zitierstil: Wuerth, J., Habjan, M., Wulle, J., Superti-Furga, G., Pichlmair, A. and Weber, F. (2018) NSs Protein of Sandfly Fever Sicilian Phlebovirus Counteracts Interferon (IFN) Induction by Masking the DNA-Binding Domain of IFN Regulatory Factor 3, Journal of Virology, 92(23), Article e01202-18. https://doi.org/10.1128/JVI.01202-18

APA-Zitierstil: Wuerth, J., Habjan, M., Wulle, J., Superti-Furga, G., Pichlmair, A., & Weber, F. (2018). NSs Protein of Sandfly Fever Sicilian Phlebovirus Counteracts Interferon (IFN) Induction by Masking the DNA-Binding Domain of IFN Regulatory Factor 3. Journal of Virology. 92(23), Article e01202-18. https://doi.org/10.1128/JVI.01202-18