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Basic Characteristics of Mutations
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Mutation Site
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R333E |
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Mutation Site Sentence
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In this study, to obtain a live vaccine strain that is attenuated by multiple mutations, we generated Ni-CE mutant, Ni-CE(G333Glu) strain, which has an Arg-to-Glu mutation at position 333 in the G protein, and examined its pathogenicity and immunogenicity. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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G |
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Standardized Encoding Gene
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RABVgp4
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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22464967
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Title
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Generation of a live rabies vaccine strain attenuated by multiple mutations and evaluation of its safety and efficacy
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Author
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Nakagawa K,Ito N,Masatani T,Abe M,Yamaoka S,Ito Y,Okadera K,Sugiyama M
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Journal
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Vaccine
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Journal Info
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2012 May 21;30(24):3610-7
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Abstract
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An amino acid substitution at position 333 in rabies virus G protein is known to determine the pathogenicity: strains with Arg or Lys at that position kill adult mice after intracerebral inoculation, whereas strains with other amino acids cause non-lethal infection. Based on those findings, attenuated rabies virus strains have been established and used for oral vaccines mainly for wild animals. However, considering the possibility of back-mutation to the virulent phenotype, a strain that is attenuated by multiple mutations not only in the G protein but also in other viral proteins would be more appropriate as a safe live vaccine. We previously demonstrated that the fixed rabies virus Ni-CE strain, which causes only transient body weight loss in adult mice after intracerebral inoculation, is mainly attenuated by mutations in the N, P and M proteins, while this strain has virulent-type Arg at position 333 in the G protein. In this study, to obtain a live vaccine strain that is attenuated by multiple mutations, we generated Ni-CE mutant, Ni-CE(G333Glu) strain, which has an Arg-to-Glu mutation at position 333 in the G protein, and examined its pathogenicity and immunogenicity. We found that, in contrast to Ni-CE strain, Ni-CE(G333Glu) strain did not cause transient body weight loss in adult mice after intracerebral inoculation. The attenuated phenotype of Ni-CE(G333Glu) strain did not change even after 10 serial intracerebral passages in suckling mice. We also demonstrated that inoculation of Ni-CE(G333Glu) strain induced virus-neutralizing antibody in immunized mice and protected the mice from lethal challenge. These results indicate that Ni-CE(G333Glu) strain is a promising candidate for development of a live rabies vaccine with a high safety level.
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Sequence Data
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-
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