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Outbreaks of sandfly fever were reported in the 19th century, during World War I, and during World War II. Currently, SFSV is recognized as one of the most widespread phleboviruses, exhibiting high seroprevalence rates in humans and domestic animals and causing a self-limiting but incapacitating disease predominantly in immunologically naive troops and travelers. We show how the nonstructural NSs protein of SFSV counteracts the upregulation of the antiviral interferon (IFN) system. SFSV NSs specifically inhibits promoter binding by IFN transcription factor 3 (IRF3), a molecular strategy which is unique among phleboviruses and, to our knowledge, among human pathogenic RNA viruses in general. This IRF3-specific and stoichiometric mechanism, greatly distinct from the ones exhibited by the highly virulent phleboviruses, correlates with the intermediate level of pathogenicity of SFSV.<\/jats:p>","DOI":"10.1128\/jvi.01202-18","type":"journal-article","created":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T01:51:02Z","timestamp":1537494662000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["NSs Protein of Sandfly Fever Sicilian Phlebovirus Counteracts Interferon (IFN) Induction by Masking the DNA-Binding Domain of IFN Regulatory Factor 3"],"prefix":"10.1128","volume":"92","author":[{"given":"Jennifer Deborah","family":"Wuerth","sequence":"first","affiliation":[{"name":"Institute for Virology, Philipps-University Marburg, Marburg, Germany"},{"name":"Institute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Habjan","sequence":"additional","affiliation":[{"name":"Innate Immunity Laboratory, Max Planck Institute of Biochemistry, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Wulle","sequence":"additional","affiliation":[{"name":"Institute for Virology, Philipps-University Marburg, Marburg, Germany"},{"name":"Institute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulio","family":"Superti-Furga","sequence":"additional","affiliation":[{"name":"CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria"},{"name":"Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Pichlmair","sequence":"additional","affiliation":[{"name":"CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria"},{"name":"Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria"},{"name":"Institute of Virology, School of Medicine, Technical University of Munich, Munich, Germany"},{"name":"Munich Partner Site, German Center for Infection Research (DZIF), Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9737-337X","authenticated-orcid":false,"given":"Friedemann","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute for Virology, Philipps-University Marburg, Marburg, Germany"},{"name":"Institute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2014.01.011"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203378"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/v8060174"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2010.05.011"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1705.101958"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/vbz.2008.0131"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.029389-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005978"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1976.25.456"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.2848.168"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01241161"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005063"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000592"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.1898"},{"key":"e_1_3_2_16_2","first-page":"287","article-title":"Sandfly fever in central Asia and Afghanistan","volume":"1","author":"Ga\u012ddamovich SY","year":"1990","unstructured":"Ga\u012ddamovich SY, Khutoretskaya NV, Asyamov YV, Tsyupa VI, Mel'nikova EE. 1990. 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