TY - JOUR KW - rabies virus KW - glycoprotein KW - lyssavirus pathogenicity AU - B Genz AU - T Nolden AU - A Negatsch AU - J Teifke AU - K-K Conzelmann AU - S Finke AB - The glycoprotein G of lyssaviruses is the major determinant of virus pathogenicity and serves as a target for immunological responses to virus infections. However, assessment of the exact contribution of lyssavirus G proteins to observed differences in the pathogenicity of lyssavirus species is challenging, since the direct comparison of natural lyssaviruses does not allow specific ascription to individual virus proteins or domains. Here we describe the generation and characterization of recombinant rabies viruses (RABV) that express chimeric G proteins comprising of a RABV cytoplasma domain fused to transmembrane and ectodomain G sequences of a virulent RABV (challenge virus standard; CVS-11) or two European bat lyssaviruses (EBLV-1 and EBLV-2). These #147;envelope-switched #148; recombinant viruses were recovered from cDNAs. Similar growth kinetics and protein expression in neuroblastoma cell cultures and successful targeting of primary neurons showed that the chimeric G proteins were able to replace the authentic G protein in a RABV based virus vector. Inoculation of six week old CD-1 mice by the intracranial (i. c.) route of infection further demonstrated that all recombinant viruses were able to spread in the brain and to induce disease. The #147;envelope-switched #148; RABV therefore represent an important tool to further investigate the influence of lyssavirus ectodomains on virus tropism, and pathogenicity. BT - Berliner und Münchener Tierärztliche Wochenschrift C1 - {"oldId":68864,"title":"Chimeric rabies viruses for trans-species comparison of lyssavirus glycoprotein ectodomain functions in virus replication and pathogenesis","topline":"","teaserText":"","content":"

Summary<\/span>
The glycoprotein G of lyssaviruses is the major determinant of virus pathogenicity and serves as a target for immunological responses to virus infections. However, assessment of the exact contribution of lyssavirus G proteins to observed differences in the pathogenicity of lyssavirus species is challenging, since the direct comparison of natural lyssaviruses does not allow specific ascription to individual virus proteins or domains. Here we describe the generation and characterization of recombinant rabies viruses (RABV) that express chimeric G proteins comprising of a RABV cytoplasma domain fused to transmembrane and ectodomain G sequences of a virulent RABV (challenge virus standard; CVS-11) or two European bat lyssaviruses (EBLV-1 and EBLV-2). These #147;envelope-switched #148; recombinant viruses were recovered from cDNAs. Similar growth kinetics and protein expression in neuroblastoma cell cultures and successful targeting of primary neurons showed that the chimeric G proteins were able to replace the authentic G protein in a RABV based virus vector. Inoculation of six week old CD-1 mice by the intracranial (i. c.) route of infection further demonstrated that all recombinant viruses were able to spread in the brain and to induce disease. The #147;envelope-switched #148; RABV therefore represent an important tool to further investigate the influence of lyssavirus ectodomains on virus tropism, and pathogenicity.

Keywords:<\/span>
rabies virus, glycoprotein, lyssavirus pathogenicity


Zusammenfassung<\/span>
Das Glykoprotein G von Lyssaviren ist die Hauptdeterminante der viralen Pathogenit\u00e4t und fungiert als Zielstruktur f\u00fcr immunologische Reaktionen auf Virusinfektionen. Die Einsch\u00e4tzung der Beteiligung von Lyssavirus G Proteinen an Unterschieden in der Pathogenit\u00e4t von Lyssavirus-Spezies ist schwierig, da der direkte Vergleich nat\u00fcrlicher Lyssaviren keine Zuordnung zu individuellen Virusproteinen oder Dom\u00e4nen erlaubt. In diesem Artikel beschreiben wir die Herstellung und Charakterisierung von rekombinanten Tollwutviren (Rabies Virus; RABV), die chim\u00e4re G Proteine exprimieren, in denen die RABV Zytoplasmadom\u00e4ne mit den Transmembran- und Ektodom\u00e4nen aus einem virulenten RABV (challenge virus standard; CVS-11) und aus zwei Europ\u00e4ische Fledermaus Lyssaviren (EBLV-1 und EBLV-2) fusioniert wurde. Diese #132;envelope-switched #147; Viren wurden von rekombinanten cDNAs generiert. Vergleichbare Wachstumskinetiken und Proteinexpression in Neuroblastoma Zellkulturen sowie die Infektion von prim\u00e4ren Neuronen zeigten, dass die chim\u00e4ren G Proteine in der Lage sind, das authentische G Protein in einem RABV basierten Virusvektor zu ersetzen. Die intrakraniale Inokulation von sechsw\u00f6chigen CD-1 M\u00e4usen zeigte weiterhin, dass alle rekombinanten Viren in der Lage waren, sich im Gehirn auszubreiten und Tollwut auszul\u00f6sen. Die #147;envelope-switched #148; RABV stellen damit wichtige Werkzeuge f\u00fcr die weitergehende Erforschung des Einflusses von Lyssavirus Ektodom\u00e4nen auf Virustropismus und Pathogenit\u00e4t dar.

Schl\u00fcsselw\u00f6rter:<\/span>
Tollwutvirus, Glykoprotein, Lyssavirus Pathogenit\u00e4t <\/p>","categories":["Open Access","Tier\u00e4rztliche Wochenschrift","Abostufe BMTW","Fachartikel","Abostufe frei"],"fromDate":"May 4, 2012 12:00:00 AM","toDate":"Dec 31, 2050 12:00:00 AM","oldUrls":["http:\/\/vetline.de\/rabies-virus-glycoprotein-lyssavirus-pathogenicity\/150\/3130\/68864","http:\/\/vetline.de\/rabies-virus-glycoprotein-lyssavirus-pathogenicity\/150\/3216\/68864"],"doiLanguage":"englisch","doiProductFormat":"Online","doiPublisher":"Schl\u00fctersche Verlagsgesellschaft mbH & Co. KG","doiSerialWorkTitle":"Berl. M\u00fcnch. Tier\u00e4rztl. Wschr.","doiDocumentUri":"http:\/\/www.vetline.de\/rabies-virus-glycoprotein-lyssavirus-pathogenicity\/150\/3130\/68864","doiSource":"Berl. M\u00fcnch. Tier\u00e4rztl. Wschr. 125: 5-6, 219-227 (2012)","doiissn":"0005-9366","doiNr":"10.2376\/0005-9366-125-219","doiFirstPage":"219","doiLastPage":"227","doiTransmitted":true,"doiAuthor":"Genz B, Nolden T, Negatsch A, Teifke JP, Conzelmann KK, Finke S","pdf":{"path":"http:\/\/data\/bmtw_2012_05_0219.pdf","title":"bmtw - Chimeric rabies viruses for trans-species","description":""},"authors":[{"firstName":"B","middleName":"","lastName":"Genz"},{"firstName":"T","middleName":"","lastName":"Nolden"},{"firstName":"A","middleName":"","lastName":"Negatsch"},{"firstName":"J","middleName":"P","lastName":"Teifke"},{"firstName":"K","middleName":"K","lastName":"Conzelmann"},{"firstName":"S","middleName":"","lastName":"Finke"}],"contentOptimised":"

Summary<\/strong>
The glycoprotein G of lyssaviruses is the major determinant of virus pathogenicity and serves as a target for immunological responses to virus infections. However, assessment of the exact contribution of lyssavirus G proteins to observed differences in the pathogenicity of lyssavirus species is challenging, since the direct comparison of natural lyssaviruses does not allow specific ascription to individual virus proteins or domains. Here we describe the generation and characterization of recombinant rabies viruses (RABV) that express chimeric G proteins comprising of a RABV cytoplasma domain fused to transmembrane and ectodomain G sequences of a virulent RABV (challenge virus standard; CVS-11) or two European bat lyssaviruses (EBLV-1 and EBLV-2). These #147;envelope-switched #148; recombinant viruses were recovered from cDNAs. Similar growth kinetics and protein expression in neuroblastoma cell cultures and successful targeting of primary neurons showed that the chimeric G proteins were able to replace the authentic G protein in a RABV based virus vector. Inoculation of six week old CD-1 mice by the intracranial (i. c.) route of infection further demonstrated that all recombinant viruses were able to spread in the brain and to induce disease. The #147;envelope-switched #148; RABV therefore represent an important tool to further investigate the influence of lyssavirus ectodomains on virus tropism, and pathogenicity.

Keywords:<\/strong>
rabies virus, glycoprotein, lyssavirus pathogenicity


Zusammenfassung<\/strong>
Das Glykoprotein G von Lyssaviren ist die Hauptdeterminante der viralen Pathogenit\u00e4t und fungiert als Zielstruktur f\u00fcr immunologische Reaktionen auf Virusinfektionen. Die Einsch\u00e4tzung der Beteiligung von Lyssavirus G Proteinen an Unterschieden in der Pathogenit\u00e4t von Lyssavirus-Spezies ist schwierig, da der direkte Vergleich nat\u00fcrlicher Lyssaviren keine Zuordnung zu individuellen Virusproteinen oder Dom\u00e4nen erlaubt. In diesem Artikel beschreiben wir die Herstellung und Charakterisierung von rekombinanten Tollwutviren (Rabies Virus; RABV), die chim\u00e4re G Proteine exprimieren, in denen die RABV Zytoplasmadom\u00e4ne mit den Transmembran- und Ektodom\u00e4nen aus einem virulenten RABV (challenge virus standard; CVS-11) und aus zwei Europ\u00e4ische Fledermaus Lyssaviren (EBLV-1 und EBLV-2) fusioniert wurde. Diese #132;envelope-switched #147; Viren wurden von rekombinanten cDNAs generiert. Vergleichbare Wachstumskinetiken und Proteinexpression in Neuroblastoma Zellkulturen sowie die Infektion von prim\u00e4ren Neuronen zeigten, dass die chim\u00e4ren G Proteine in der Lage sind, das authentische G Protein in einem RABV basierten Virusvektor zu ersetzen. Die intrakraniale Inokulation von sechsw\u00f6chigen CD-1 M\u00e4usen zeigte weiterhin, dass alle rekombinanten Viren in der Lage waren, sich im Gehirn auszubreiten und Tollwut auszul\u00f6sen. Die #147;envelope-switched #148; RABV stellen damit wichtige Werkzeuge f\u00fcr die weitergehende Erforschung des Einflusses von Lyssavirus Ektodom\u00e4nen auf Virustropismus und Pathogenit\u00e4t dar.

Schl\u00fcsselw\u00f6rter:<\/strong>
Tollwutvirus, Glykoprotein, Lyssavirus Pathogenit\u00e4t <\/p>","primaryLanguage":"englisch","summary":"The glycoprotein G of lyssaviruses is the major determinant of virus pathogenicity and serves as a target for immunological responses to virus infections. However, assessment of the exact contribution of lyssavirus G proteins to observed differences in the pathogenicity of lyssavirus species is challenging, since the direct comparison of natural lyssaviruses does not allow specific ascription to individual virus proteins or domains. Here we describe the generation and characterization of recombinant rabies viruses (RABV) that express chimeric G proteins comprising of a RABV cytoplasma domain fused to transmembrane and ectodomain G sequences of a virulent RABV (challenge virus standard; CVS-11) or two European bat lyssaviruses (EBLV-1 and EBLV-2). These #147;envelope-switched #148; recombinant viruses were recovered from cDNAs. Similar growth kinetics and protein expression in neuroblastoma cell cultures and successful targeting of primary neurons showed that the chimeric G proteins were able to replace the authentic G protein in a RABV based virus vector. Inoculation of six week old CD-1 mice by the intracranial (i. c.) route of infection further demonstrated that all recombinant viruses were able to spread in the brain and to induce disease. The #147;envelope-switched #148; RABV therefore represent an important tool to further investigate the influence of lyssavirus ectodomains on virus tropism, and pathogenicity.","keywords":["rabies virus","glycoprotein","lyssavirus pathogenicity"],"zusammenfassung":"Das Glykoprotein G von Lyssaviren ist die Hauptdeterminante der viralen Pathogenit\u00e4t und fungiert als Zielstruktur f\u00fcr immunologische Reaktionen auf Virusinfektionen. Die Einsch\u00e4tzung der Beteiligung von Lyssavirus G Proteinen an Unterschieden in der Pathogenit\u00e4t von Lyssavirus-Spezies ist schwierig, da der direkte Vergleich nat\u00fcrlicher Lyssaviren keine Zuordnung zu individuellen Virusproteinen oder Dom\u00e4nen erlaubt. In diesem Artikel beschreiben wir die Herstellung und Charakterisierung von rekombinanten Tollwutviren (Rabies Virus; RABV), die chim\u00e4re G Proteine exprimieren, in denen die RABV Zytoplasmadom\u00e4ne mit den Transmembran- und Ektodom\u00e4nen aus einem virulenten RABV (challenge virus standard; CVS-11) und aus zwei Europ\u00e4ische Fledermaus Lyssaviren (EBLV-1 und EBLV-2) fusioniert wurde. Diese #132;envelope-switched #147; Viren wurden von rekombinanten cDNAs generiert. Vergleichbare Wachstumskinetiken und Proteinexpression in Neuroblastoma Zellkulturen sowie die Infektion von prim\u00e4ren Neuronen zeigten, dass die chim\u00e4ren G Proteine in der Lage sind, das authentische G Protein in einem RABV basierten Virusvektor zu ersetzen. Die intrakraniale Inokulation von sechsw\u00f6chigen CD-1 M\u00e4usen zeigte weiterhin, dass alle rekombinanten Viren in der Lage waren, sich im Gehirn auszubreiten und Tollwut auszul\u00f6sen. Die #147;envelope-switched #148; RABV stellen damit wichtige Werkzeuge f\u00fcr die weitergehende Erforschung des Einflusses von Lyssavirus Ektodom\u00e4nen auf Virustropismus und Pathogenit\u00e4t dar.","schluesselwoerter":["Tollwutvirus","Glykoprotein","Lyssavirus Pathogenit\u00e4t"],"translatedTitle":"","abstractE":"The glycoprotein G of lyssaviruses is the major determinant of virus pathogenicity and serves as a target for immunological responses to virus infections. However, assessment of the exact contribution of lyssavirus G proteins to observed differences in the pathogenicity of lyssavirus species is challenging, since the direct comparison of natural lyssaviruses does not allow specific ascription to individual virus proteins or domains. Here we describe the generation and characterization of recombinant rabies viruses (RABV) that express chimeric G proteins comprising of a RABV cytoplasma domain fused to transmembrane and ectodomain G sequences of a virulent RABV (challenge virus standard; CVS-11) or two European bat lyssaviruses (EBLV-1 and EBLV-2). These #147;envelope-switched #148; recombinant viruses were recovered from cDNAs. Similar growth kinetics and protein expression in neuroblastoma cell cultures and successful targeting of primary neurons showed that the chimeric G proteins were able to replace the authentic G protein in a RABV based virus vector. Inoculation of six week old CD-1 mice by the intracranial (i. c.) route of infection further demonstrated that all recombinant viruses were able to spread in the brain and to induce disease. The #147;envelope-switched #148; RABV therefore represent an important tool to further investigate the influence of lyssavirus ectodomains on virus tropism, and pathogenicity.","date":{"year":2012,"date":"05\/2012","accepted":"2012-05-04"},"volume":"125","openAccess":true,"journal":"Berliner und M\u00fcnchener Tier\u00e4rztliche Wochenschrift","titleImageId":944,"pages":"219-227","redirects":["rabies-virus-glycoprotein-lyssavirus-pathogenicity\/150\/3130\/68864","rabies-virus-glycoprotein-lyssavirus-pathogenicity\/150\/3216\/68864"],"tierartCategories":[],"artikelartCategories":["Open Access","Tier\u00e4rztliche Wochenschrift","Abostufe BMTW","Fachartikel","Abostufe frei"]} CY - Hannover DA - 05/2012 DO - 10.2376/0005-9366-125-219 LA - English N2 - The glycoprotein G of lyssaviruses is the major determinant of virus pathogenicity and serves as a target for immunological responses to virus infections. However, assessment of the exact contribution of lyssavirus G proteins to observed differences in the pathogenicity of lyssavirus species is challenging, since the direct comparison of natural lyssaviruses does not allow specific ascription to individual virus proteins or domains. Here we describe the generation and characterization of recombinant rabies viruses (RABV) that express chimeric G proteins comprising of a RABV cytoplasma domain fused to transmembrane and ectodomain G sequences of a virulent RABV (challenge virus standard; CVS-11) or two European bat lyssaviruses (EBLV-1 and EBLV-2). These #147;envelope-switched #148; recombinant viruses were recovered from cDNAs. Similar growth kinetics and protein expression in neuroblastoma cell cultures and successful targeting of primary neurons showed that the chimeric G proteins were able to replace the authentic G protein in a RABV based virus vector. Inoculation of six week old CD-1 mice by the intracranial (i. c.) route of infection further demonstrated that all recombinant viruses were able to spread in the brain and to induce disease. The #147;envelope-switched #148; RABV therefore represent an important tool to further investigate the influence of lyssavirus ectodomains on virus tropism, and pathogenicity. PB - Schlütersche Verlagsgesellschaft mbH & Co. KG PP - Hannover PY - 2012 SP - 219 EP - 227 T1 - Chimeric rabies viruses for trans-species comparison of lyssavirus glycoprotein ectodomain functions in virus replication and pathogenesis T2 - Berliner und Münchener Tierärztliche Wochenschrift TI - Chimeric rabies viruses for trans-species comparison of lyssavirus glycoprotein ectodomain functions in virus replication and pathogenesis VL - 125 SN - 0005-9366 ER -