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Basic Characteristics of Mutations
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Mutation Site
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G82R |
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Mutation Site Sentence
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We also evaluated whether these target sequences could augment safety of an LAV encoding a known attenuating mutation, E2 G82R. |
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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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E2 |
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Standardized Encoding Gene
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E2
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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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Chikungunya Fever
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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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35196388
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Title
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Chikungunya Virus Vaccine Candidate Incorporating Synergistic Mutations Is Attenuated and Protects Against Virulent Virus Challenge
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Author
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Lentscher AJ,McAllister N,Griswold KA,Martin JL,Welsh OL,Sutherland DM,Silva LA,Dermody TS
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Journal
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The Journal of infectious diseases
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Journal Info
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2023 Feb 1;227(3):457-465
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Abstract
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BACKGROUND: Chikungunya virus (CHIKV) is an arbovirus that periodically emerges to cause large epidemics of arthritic disease. Although the robust immunity elicited by live-attenuated virus (LAV) vaccine candidates makes them attractive, CHIKV vaccine development has been hampered by a high threshold for acceptable adverse events. METHODS: We evaluated the vaccine potential of a recently described LAV, skeletal muscle-restricted virus (SKE), that exhibits diminished replication in skeletal muscle due to insertion of target sequences for skeletal muscle-specific miR-206. We also evaluated whether these target sequences could augment safety of an LAV encoding a known attenuating mutation, E2 G82R. Attenuation of viruses containing these mutations was compared with a double mutant, SKE G82R. RESULTS: SKE was attenuated in both immunodeficient and immunocompetent mice and induced a robust neutralizing antibody response, indicating its vaccine potential. However, only SKE G82R elicited diminished swelling in immunocompetent mice at early time points postinoculation, indicating that these mutations synergistically enhance safety of the vaccine candidate. CONCLUSIONS: These data suggest that restriction of LAV replication in skeletal muscle enhances tolerability of reactogenic vaccine candidates and may improve the rational design of CHIKV vaccines.
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Sequence Data
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-
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