{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:43:33Z","timestamp":1790480613103,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009038","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000}}],"reference-count":83,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T00:00:00Z","timestamp":1605484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SPP 1596\/KO 1579\/9-2"],"award-info":[{"award-number":["SPP 1596\/KO 1579\/9-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KO 1579\/12-1"],"award-info":[{"award-number":["KO 1579\/12-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010771","name":"Bundesanstalt f\u00fcr Landwirtschaft und Ern\u00e4hrung","doi-asserted-by":"publisher","award":["2816HS008"],"award-info":[{"award-number":["2816HS008"]}],"id":[{"id":"10.13039\/501100010771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Infections with emerging and re-emerging arboviruses are of increasing concern for global health. Tick-transmitted RNA viruses of the genus\n                    <jats:italic>Thogotovirus<\/jats:italic>\n                    in the\n                    <jats:italic>Orthomyxoviridae<\/jats:italic>\n                    family have considerable zoonotic potential, as indicated by the recent emergence of Bourbon virus in the USA. To successfully infect humans, arboviruses have to escape the restrictive power of the interferon defense system. This is exemplified by the high sensitivity of thogotoviruses to the antiviral action of the interferon-induced myxovirus resistance protein A (MxA) that inhibits the polymerase activity of incoming viral ribonucleoprotein complexes. Acquiring resistance to human MxA would be expected to enhance the zoonotic potential of these pathogens. Therefore, we screened a panel of 10 different thogotovirus isolates obtained from various parts of the world for their sensitivity to MxA. A single isolate from Nigeria, Jos virus, showed resistance to the antiviral action of MxA in cell culture and in MxA-transgenic mice, whereas the prototypic Sicilian isolate SiAr126 was fully MxA-sensitive. Further analysis identified two amino acid substitutions (G327R and R328V) in the viral nucleoprotein as determinants for MxA resistance. Importantly, when introduced into SiAr126, the R328V mutation resulted in complete MxA escape of the recombinant virus, without causing any viral fitness loss. The escape mutation abolished viral nucleoprotein recognition by MxA and allowed unhindered viral growth in MxA-expressing cells and in MxA-transgenic mice. These findings demonstrate that thogotoviruses can overcome the species barrier by escaping MxA restriction and reveal that these tick-transmitted viruses may have a greater zoonotic potential than previously suspected.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009038","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T13:35:31Z","timestamp":1605533731000},"page":"e1009038","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Tick-transmitted thogotovirus gains high virulence by a single MxA escape mutation in the viral nucleoprotein"],"prefix":"10.1371","volume":"16","author":[{"given":"Jonas","family":"Fuchs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Oschwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0187-559X","authenticated-orcid":true,"given":"Georg","family":"Kochs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,16]]},"reference":[{"key":"ppat.1009038.ref001","first-page":"749","article-title":"Family orthomyxoviridae","author":"JW McCauley","year":"2012","journal-title":"Virus Taxon ninth Rep Int Comm Taxon viruses"},{"key":"ppat.1009038.ref002","article-title":"Changes to taxonomy and the International Code of Virus Classification and Nomenclature ratified by the International Committee on Taxonomy of Viruses (2018)","author":"AMQ King","year":"2018","journal-title":"Arch Virol"},{"key":"ppat.1009038.ref003","article-title":"Estimates of global seasonal influenza-associated respiratory mortality: a modelling study","author":"AD Iuliano","year":"2018","journal-title":"Lancet"},{"key":"ppat.1009038.ref004","article-title":"Dhori virus, a new agent isolated from Hyalomma dromedarii in India","author":"CR Anderson","year":"1973","journal-title":"Indian J Med Res"},{"key":"ppat.1009038.ref005","article-title":"Bourbon Virus in Wild and Domestic Animals, Missouri, USA, 2012\u20132013","author":"KC Jackson","year":"2019","journal-title":"Emerg Infect Dis"},{"key":"ppat.1009038.ref006","article-title":"Antibodies to congo-crimean haemorrhagic fever, Dhori, Thogoto and Bhanja viruses in southern Portugal","author":"AR Filipe","year":"1985","journal-title":"Acta Virol"},{"key":"ppat.1009038.ref007","article-title":"A serological survey for Thogoto virus in humans, domestic mammals, and rats in Egypt","author":"MA Darwish","year":"1979","journal-title":"J Egypt Public Health Assoc"},{"key":"ppat.1009038.ref008","article-title":"Epidemiological study of thogoto and dhori virus infection in people bitten by ticks, and in sheep, in an area of Northern Spain","author":"L Lled\u00f3","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"ppat.1009038.ref009","article-title":"Abortion in sheep caused by Thogoto virus","author":"FG Davies","year":"1984","journal-title":"Vet Rec"},{"key":"ppat.1009038.ref010","article-title":"Tick-borne viruses structurally similar to orthomyxoviruses","author":"JPM Clerx","year":"1983","journal-title":"Virology"},{"key":"ppat.1009038.ref011","article-title":"In vivo reconstitution of active Thogoto virus polymerase: assays for the compatibility with other orthomyxovirus core proteins and template RNAs","author":"F Weber","year":"1998","journal-title":"Virus Res"},{"key":"ppat.1009038.ref012","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nrmicro3367","article-title":"At the centre: influenza A virus ribonucleoproteins","volume":"13","author":"AJ Eisfeld","year":"2015","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1009038.ref013","article-title":"Trafficking of viral genomic RNA into and out of the nucleus: Influenza, Thogoto and Borna disease viruses","author":"JF Cros","year":"2003","journal-title":"Virus Res"},{"key":"ppat.1009038.ref014","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.4269\/ajtmh.1986.35.1256","article-title":"Experimental Studies on the Transmission Cycle of Thogoto Virus, a Candidate Orthomyxovirus, in Rhipicephalus appendiculatus","volume":"35","author":"CR Davies","year":"1986","journal-title":"Am J Trop Med Hyg"},{"key":"ppat.1009038.ref015","article-title":"Arthropod-borne viral infections of man in nigeria, 1964\u20131970","author":"DL Moore","year":"1975","journal-title":"Ann Trop Med Parasitol"},{"key":"ppat.1009038.ref016","article-title":"Dhori virus, a causative agent of human disease. Five cases of laboratory infection","author":"AM Butenko","year":"1987","journal-title":"Vopr Virusol"},{"key":"ppat.1009038.ref017","article-title":"Therapeutic efficacy of favipiravir against Bourbon virus in mice","author":"TL Bricker","year":"2019","journal-title":"PLoS Pathog"},{"key":"ppat.1009038.ref018","article-title":"Novel Thogotovirus associated with febrile illness and death, united states, 2014","author":"OI Kosoy","year":"2015","journal-title":"Emerg Infect Dis"},{"key":"ppat.1009038.ref019","article-title":"Surveillance for tick-borne viruses near the location of a fatal human case of bourbon virus (Family Orthomyxoviridae: Genus Thogotovirus) in Eastern Kansas, 2015","author":"HM Savage","year":"2018","journal-title":"J Med Entomol"},{"key":"ppat.1009038.ref020","article-title":"Bourbon virus in field-collected ticks, Missouri, USA","author":"HM Savage","year":"2017","journal-title":"Emerg Infect Dis"},{"key":"ppat.1009038.ref021","article-title":"Indirect Evidence of Bourbon Virus (Thogotovirus, Orthomyxoviridae) Infection in North Carolina","author":"N Komar","year":"2020","journal-title":"N C Med J"},{"key":"ppat.1009038.ref022","article-title":"Interferon-Stimulated Genes: A Complex Web of Host Defenses","author":"WM Schneider","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"ppat.1009038.ref023","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1128\/MMBR.00024-13","article-title":"Mx proteins: antiviral gatekeepers that restrain the uninvited","volume":"77","author":"J Verhelst","year":"2013","journal-title":"Microbiol Mol Biol Rev"},{"key":"ppat.1009038.ref024","article-title":"Mx GTPases: Dynamin-like antiviral machines of innate immunity","author":"O Haller","year":"2015","journal-title":"Trends in Microbiology"},{"key":"ppat.1009038.ref025","article-title":"Role of nucleotide binding and GTPase domain dimerization in dynamin-like myxovirus resistance protein a for GTPase activation and antiviral activity","author":"A Dick","year":"2015","journal-title":"J Biol Chem"},{"key":"ppat.1009038.ref026","article-title":"GTP-bound human MxA protein interacts with the nucleocapsids of Thogoto virus (orthomyxoviridae)","author":"G Kochs","year":"1999","journal-title":"J Biol Chem"},{"key":"ppat.1009038.ref027","article-title":"Structural requirements for the antiviral activity of the human MxA protein against Thogoto and influenza A virus","author":"C Patzina","year":"2014","journal-title":"J Biol Chem"},{"key":"ppat.1009038.ref028","article-title":"Interferon-induced human MxA GTPase blocks nuclear import of thogoto virus nucleocapsids","author":"G Kochs","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1009038.ref029","article-title":"In vivo evasion of MxA by avian influenza viruses requires human signature in the viral nucleoprotein","author":"CM Deeg","year":"2017","journal-title":"J Exp Med"},{"key":"ppat.1009038.ref030","article-title":"Enhanced virus resistance of transgenic mice 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Filipe","year":"1979","journal-title":"Intervirology"},{"key":"ppat.1009038.ref036","article-title":"Batken virus, a new arbovirus isolated from ticks and mosquitoes in Kirghiz S.S.R","author":"DK Lvov","year":"1974","journal-title":"Arch Gesamte Virusforsch"},{"key":"ppat.1009038.ref037","article-title":"Characterization of a novel thogotovirus isolated from Amblyomma testudinarium ticks in Ehime, Japan: A significant phylogenetic relationship to Bourbon virus","author":"H Ejiri","year":"2018","journal-title":"Virus Res"},{"key":"ppat.1009038.ref038","article-title":"Isolation of the Thogoto virus from a Haemaphysalis longicornis in Kyoto City, Japan","author":"K Yoshii","year":"2015","journal-title":"J Gen Virol"},{"key":"ppat.1009038.ref039","article-title":"Human MxA protein inhibits tick-borne Thogoto virus but not Dhori virus","author":"M Frese","year":"1995","journal-title":"J Virol"},{"key":"ppat.1009038.ref040","article-title":"Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation","author":"P Staeheli","year":"1988","journal-title":"Mol Cell Biol"},{"key":"ppat.1009038.ref041","article-title":"Polyclonal and monoclonal antibodies to the interferon-inducible protein Mx of influenza virus-resistant mice","author":"P Staeheli","year":"1985","journal-title":"J Biol Chem"},{"key":"ppat.1009038.ref042","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1099\/0022-1317-68-3-945","article-title":"A recombinant human interferon-\u03b1 B\/D hybrid with a broad host-range","volume":"68","author":"MA Horisberger","year":"1987","journal-title":"J Gen Virol"},{"key":"ppat.1009038.ref043","article-title":"Evolution-guided identification of antiviral specificity determinants in the broadly acting interferon-induced innate immunity factor MxA","author":"PS Mitchell","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ppat.1009038.ref044","article-title":"Pandemic Influenza A Viruses Escape from Restriction by Human MxA through Adaptive Mutations in the Nucleoprotein","author":"B M\u00e4nz","year":"2013","journal-title":"PLoS Pathog"},{"key":"ppat.1009038.ref045","article-title":"The Human Interferon-Induced MxA Protein Inhibits Early Stages of Influenza A Virus Infection by Retaining the Incoming Viral Genome in the Cytoplasm","author":"H Xiao","year":"2013","journal-title":"J Virol"},{"key":"ppat.1009038.ref046","article-title":"Mechanism of human MxA protein action: variants with changed antiviral properties","author":"T Z\u00fcrcher","year":"1992","journal-title":"EMBO J"},{"key":"ppat.1009038.ref047","article-title":"Combinatorial mutagenesis of rapidly evolving residues yields super-restrictor antiviral proteins","author":"R Col\u00f3n-Thillet","year":"2019","journal-title":"PLOS Biol"},{"key":"ppat.1009038.ref048","article-title":"Evolution and Antiviral Specificities of Interferon-Induced Mx Proteins of Bats against Ebola, Influenza, and Other RNA Viruses","author":"J Fuchs","year":"2017","journal-title":"J Virol"},{"key":"ppat.1009038.ref049","article-title":"NS1-mediated delay of type I interferon induction contributes to influenza A virulence in ferrets","author":"I Meunier","year":"2011","journal-title":"J Gen Virol"},{"key":"ppat.1009038.ref050","article-title":"High yields of influenza A virus in Madin-Darby canine kidney cells are promoted by an insufficient interferon-induced antiviral state","author":"C Seitz","year":"2010","journal-title":"J Gen Virol"},{"key":"ppat.1009038.ref051","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.nbd.2005.08.015","article-title":"Expression of the interferon-alpha\/beta-inducible bovine Mx1 dynamin interferes with replication of rabies virus","volume":"21","author":"M Leroy","year":"2006","journal-title":"Neurobiol Dis"},{"key":"ppat.1009038.ref052","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1089\/jir.2018.0157","article-title":"Anti-Influenza A Virus Activities of Type I\/III Interferons-Induced Mx1 GTPases from Different Mammalian Species","volume":"39","author":"P Dam Van","year":"2019","journal-title":"J Interf Cytokine Res"},{"key":"ppat.1009038.ref053","article-title":"Human MxA protein protects mice lacking a functional alpha\/beta interferon system against La crosse virus and other lethal viral infections","author":"HP Hefti","year":"1999","journal-title":"J Virol"},{"key":"ppat.1009038.ref054","article-title":"Interferon-\u03b1 inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway","author":"M Frese","year":"2001","journal-title":"J Gen Virol"},{"key":"ppat.1009038.ref055","article-title":"Genomic and antigenic characterization of Jos virus","author":"AV Bussetti","year":"2012","journal-title":"J Gen Virol"},{"key":"ppat.1009038.ref056","article-title":"Structure of Myxovirus Resistance Protein A Reveals Intra- and Intermolecular Domain Interactions Required for the Antiviral Function","author":"S Gao","year":"2011","journal-title":"Immunity"},{"key":"ppat.1009038.ref057","article-title":"Structural basis of oligomerization in the stalk region of dynamin-like MxA","author":"S Gao","year":"2010","journal-title":"Nature"},{"key":"ppat.1009038.ref058","article-title":"Myxovirus Resistance Gene A (MxA) Expression Suppresses Influenza A Virus Replication in Alpha Interferon-Treated Primate Cells","author":"SR Matzinger","year":"2013","journal-title":"J Virol"},{"key":"ppat.1009038.ref059","article-title":"Destabilized adaptive influenza variants critical for innate immune system escape are potentiated by host chaperones","author":"AM Phillips","year":"2018","journal-title":"PLoS Biol"},{"key":"ppat.1009038.ref060","article-title":"Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import","author":"V G\u00f6tz","year":"2016","journal-title":"Sci Rep"},{"key":"ppat.1009038.ref061","article-title":"Structure of the influenza virus A H5N1 nucleoprotein: Implications for RNA binding, oligomerization, and vaccine design","author":"AKL Ng","year":"2008","journal-title":"FASEB J"},{"key":"ppat.1009038.ref062","article-title":"Sequence in the Influenza A Virus Nucleoprotein Required for Viral Polymerase Binding and RNA Synthesis","author":"JK Marklund","year":"2012","journal-title":"J Virol"},{"key":"ppat.1009038.ref063","article-title":"The mechanism by which influenza A virus nucleoprotein forms oligomers and binds RNA","author":"Q Ye","year":"2006","journal-title":"Nature"},{"key":"ppat.1009038.ref064","article-title":"The structure of native influenza virion ribonucleoproteins","author":"R Arranz","year":"2012","journal-title":"Science (80-)"},{"key":"ppat.1009038.ref065","article-title":"Organization of the influenza virus replication machinery","author":"A Moeller","year":"2012","journal-title":"Science (80-)"},{"key":"ppat.1009038.ref066","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/356121a0","article-title":"Mammalian phytogeny: shaking the tree","volume":"356","author":"MJ Novacek","year":"1992","journal-title":"Nature"},{"key":"ppat.1009038.ref067","first-page":"28","article-title":"Surgey of tick-borne arboviruses in the Central African Republic (1973\u20131974). Isolation of Dugbe, CHF\/Congo, Jos and Bhanja viruses","volume":"69","author":"P Sureau","year":"1976","journal-title":"Bull Soc Pathol Exot Filiales"},{"key":"ppat.1009038.ref068","article-title":"Dhori virus (Orthomyxoviridae: Thogotovirus) infection in mice: A model of the pathogenesis of severe orthomyxovirus infection","author":"RI Mateo","year":"2007","journal-title":"Am J Trop Med Hyg"},{"key":"ppat.1009038.ref069","article-title":"Mx1 but Not MxA Confers Resistance against Tick-Borne Dhori Virus in Mice","author":"R Thimme","year":"1995","journal-title":"Virology"},{"key":"ppat.1009038.ref070","article-title":"Tick-borne Thogoto virus infection in mice is inhibited by the orthomyxovirus resistance gene product Mx1","author":"O Haller","year":"1995","journal-title":"J Virol"},{"key":"ppat.1009038.ref071","article-title":"Mx1-based resistance to Thogoto virus in A2G mice is bypassed in tick- mediated virus delivery","author":"JT Dessens","year":"1998","journal-title":"J Virol"},{"key":"ppat.1009038.ref072","article-title":"Mutations in murine mx1: Effects on localization and antiviral activity","author":"EA Garber","year":"1993","journal-title":"Virology"},{"key":"ppat.1009038.ref073","article-title":"Interferon induces a unique protein in mouse cells bearing a gene for resistance to influenza virus","author":"MA Horisberger","year":"1983","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1009038.ref074","article-title":"Human and mouse Mx proteins inhibit different steps of the influenza virus multiplication cycle","author":"J Pavlovic","year":"1992","journal-title":"J Virol"},{"key":"ppat.1009038.ref075","article-title":"Nuclear localization of mouse Mx1 protein is necessary for inhibition of influenza virus","author":"T Zurcher","year":"1992","journal-title":"J Virol"},{"key":"ppat.1009038.ref076","article-title":"Interferon-Inducible Protein Mx1 Inhibits Influenza Virus by Interfering with Functional Viral Ribonucleoprotein Complex Assembly","author":"J Verhelst","year":"2012","journal-title":"J Virol"},{"key":"ppat.1009038.ref077","article-title":"Function of the mouse Mx1 protein is inhibited by overexpression of the PB2 protein of influenza virus","author":"AM Stranden","year":"1993","journal-title":"Virology"},{"key":"ppat.1009038.ref078","article-title":"Growth of human hepatoma cell lines with differentiated functions in chemically defined medium","author":"H Nakabayashi","year":"1982","journal-title":"Cancer Res"},{"key":"ppat.1009038.ref079","article-title":"Human MxB Protein Is a Pan-herpesvirus Restriction Factor","author":"M Schilling","year":"2018","journal-title":"J Virol"},{"key":"ppat.1009038.ref080","article-title":"The central interactive region of human MxA GTPase is involved in GTPase activation and interaction with viral target structures","author":"F Flohr","year":"1999","journal-title":"FEBS Lett"},{"key":"ppat.1009038.ref081","article-title":"The Interferon Antagonist ML Protein of Thogoto Virus Targets General Transcription Factor IIB","author":"C Vogt","year":"2008","journal-title":"J Virol"},{"key":"ppat.1009038.ref082","article-title":"SWISS-MODEL: Homology modelling of protein structures and complexes","author":"A Waterhouse","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"ppat.1009038.ref083","article-title":"A classical bipartite nuclear localization signal on Thogoto and influenza A virus nucleoproteins","author":"F Weber","year":"1998","journal-title":"Virology"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1009038","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T14:32:46Z","timestamp":1606746766000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009038"}},"subtitle":[],"editor":[{"given":"Carolina B.","family":"Lopez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,11,16]]},"references-count":83,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1009038","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,16]]}}}