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Basic Characteristics of Mutations
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Mutation Site
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M19A |
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Mutation Site Sentence
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Deletion and mutation studies showed that the N-terminus of NS5 was involved in the MTP association, and a single point mutation of NS5 residue 19 from methionine to alanine (NS5-M19A) reduced its binding ability with MTP. |
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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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NS5 |
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Standardized Encoding Gene
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NS5
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Genotype/Subtype
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- |
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Viral Reference
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AF014161
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Functional Impact and Mechanisms
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Disease
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Cell line
JEV Infection
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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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25816318
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Title
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Japanese encephalitis virus nonstructural protein NS5 interacts with mitochondrial trifunctional protein and impairs fatty acid beta-oxidation
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Author
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Kao YT,Chang BL,Liang JJ,Tsai HJ,Lee YL,Lin RJ,Lin YL
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Journal
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PLoS pathogens
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Journal Info
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2015 Mar 27;11(3):e1004750
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Abstract
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Infection with Japanese encephalitis virus (JEV) can induce the expression of pro-inflammatory cytokines and cause acute encephalitis in humans. beta-oxidation breaks down fatty acids for ATP production in mitochondria, and impaired beta-oxidation can induce pro-inflammatory cytokine expression. To address the role of fatty-acid beta-oxidation in JEV infection, we measured the oxygen consumption rate of mock- and JEV-infected cells cultured with or without long chain fatty acid (LCFA) palmitate. Cells with JEV infection showed impaired LCFA beta-oxidation and increased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) expression. JEV nonstructural protein 5 (NS5) interacted with hydroxyacyl-CoA dehydrogenase alpha and beta subunits, two components of the mitochondrial trifunctional protein (MTP) involved in LCFA beta-oxidation, and NS5 proteins were detected in mitochondria and co-localized with MTP. LCFA beta-oxidation was impaired and higher cytokines were induced in cells overexpressing NS5 protein as compared with control cells. Deletion and mutation studies showed that the N-terminus of NS5 was involved in the MTP association, and a single point mutation of NS5 residue 19 from methionine to alanine (NS5-M19A) reduced its binding ability with MTP. The recombinant JEV with NS5-M19A mutation (JEV-NS5-M19A) was less able to block LCFA beta-oxidation and induced lower levels of IL-6 and TNF-alpha than wild-type JEV. Moreover, mice challenged with JEV-NS5-M19A showed less neurovirulence and neuroinvasiveness. We identified a novel function of JEV NS5 in viral pathogenesis by impairing LCFA beta-oxidation and inducing cytokine expression by association with MTP.
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Sequence Data
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-
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