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The results of our studies confirmed that the R333Q mutation in the glycoprotein (G<jats:sub>R333Q<\/jats:sub>) is crucial for the attenuation of Flury RV in mice. The R333Q mutation is stably maintained in the HEP genome background but not in the LEP genome background during replication in mouse brain tissue or cell culture. Further investigation using chimeric viruses revealed that the polymerase L gene determines the genetic stability of the G<jats:sub>R333Q<\/jats:sub>mutation during replication. Moreover, a recombinant RV containing the LEP G protein with the R333Q mutation and the HEP L gene showed significant attenuation, genetic stability, enhancement of apoptosis, and immunogenicity. These results indicate that attenuation of the RV Flury strain results from the coevolution of G and L elements and provide important information for the generation of safer and more effective modified live rabies vaccine.<\/jats:p>","DOI":"10.1128\/jvi.00787-10","type":"journal-article","created":{"date-parts":[[2010,6,11]],"date-time":"2010-06-11T02:17:16Z","timestamp":1276222636000},"page":"8926-8936","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Molecular Basis of Neurovirulence of Flury Rabies Virus Vaccine Strains: Importance of the Polymerase and the Glycoprotein R333Q Mutation"],"prefix":"10.1128","volume":"84","author":[{"given":"Lihong","family":"Tao","sequence":"first","affiliation":[{"name":"Veterinary Public Health Laboratory of Ministry of Agriculture and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinying","family":"Ge","sequence":"additional","affiliation":[{"name":"Veterinary Public Health Laboratory of Ministry of Agriculture and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Veterinary Public Health Laboratory of Ministry of Agriculture and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyue","family":"Zhai","sequence":"additional","affiliation":[{"name":"Veterinary Public Health Laboratory of Ministry of Agriculture and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Hua","sequence":"additional","affiliation":[{"name":"Veterinary Public Health Laboratory of Ministry of Agriculture and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Veterinary Public Health Laboratory of Ministry of Agriculture and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongni","family":"Kong","sequence":"additional","affiliation":[{"name":"Veterinary Public Health Laboratory of Ministry of Agriculture and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinglai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Rollins Research Center, Atlanta, Georgia 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualan","family":"Chen","sequence":"additional","affiliation":[{"name":"Veterinary Public Health Laboratory of Ministry of Agriculture and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigao","family":"Bu","sequence":"additional","affiliation":[{"name":"Veterinary Public Health Laboratory of Ministry of Agriculture and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/294275a0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/79470"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.27.3.1012-1022.1980"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.35.3.682-693.1980"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(90)90433-R"},{"key":"e_1_3_2_7_2","first-page":"45","volume":"292","year":"2005","unstructured":"Dietzschold, B., M. 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