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A common flavivirus trait is the antagonism of interferon (IFN) signaling to enhance viral replication and spread. We report that like ZIKV NS5 and DENV NS5, YFV NS5 binds human STAT2 (hSTAT2) but not mouse STAT2 (mSTAT2), a type I IFN (IFN-\u03b1\/\u03b2) pathway component. Additionally, we show that contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, YFV NS5 is unable to interact with hSTAT2 in murine cells. We demonstrate that mSTAT2 restricts YFV replication in mice and that this correlates with a lack of IFN-\u03b1\/\u03b2-induced YFV NS5 ubiquitination in murine cells. The lack of suitable animal models limits flavivirus pathogenesis, vaccine, and drug research. These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses.<\/jats:p>","DOI":"10.1128\/jvi.00151-19","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T06:52:01Z","timestamp":1556693521000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Host-Specific NS5 Ubiquitination Determines Yellow Fever Virus Tropism"],"prefix":"10.1128","volume":"93","author":[{"given":"Lisa","family":"Miorin","sequence":"first","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"},{"name":"Icahn School of Medicine at Mount Sinai, Global Health and Emerging Pathogens Institute, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maudry","family":"Laurent-Rolle","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Yale University, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pisanelli","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"},{"name":"Icahn School of Medicine at Mount Sinai, Global Health and Emerging Pathogens Institute, New York, New York, USA"},{"name":"Department of Veterinary Medicine and Animal Production, University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre Hendrick","family":"Co","sequence":"additional","affiliation":[{"name":"Department of Biology, Queens College, City University of New York, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4008-503X","authenticated-orcid":false,"given":"Randy A.","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"},{"name":"Icahn School of Medicine at Mount Sinai, Global Health and Emerging Pathogens Institute, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"Garc\u00eda-Sastre","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA"},{"name":"Icahn School of Medicine at Mount Sinai, Global Health and Emerging Pathogens Institute, New York, New York, USA"},{"name":"Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7387-6351","authenticated-orcid":false,"given":"Juliet","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Plant Pathology, University of California, Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/532155a"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2016.1180250"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2015.1022700"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001638"},{"key":"e_1_3_2_7_2","unstructured":"World Health Organization. 2018. 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