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Basic Characteristics of Mutations
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Mutation Site
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R393N |
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Mutation Site Sentence
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Deletion of betaNLS, alpha/betaNLS, or both as well as R393A and R393N mutations severely impaired NS5 nuclear import and consequently conferred NS5 degradation. |
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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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-
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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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32056710
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Title
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Zika virus NS5 nuclear accumulation is protective of protein degradation and is required for viral RNA replication
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Author
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Ji W,Luo G
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Journal
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Virology
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Journal Info
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2020 Feb;541:124-135
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Abstract
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Zika virus (ZIKV) nonstructural protein 5 (NS5) is a multifunctional protein possessing methyltransferase and RNA-dependent RNA polymerase activities. In the present study, we have carried out an extensive mutagenesis analysis to determine the importance of nuclear localization sequences (NLS) of NS5 in its nuclear accumulation and ZIKV replication. Deletion mutagenesis analysis demonstrated that the bipartite NLS consisting of importin beta1 (betaNLS) and importin alpha/beta-recognized NLS (alpha/betaNLS) is required for NS5 nuclear accumulation. Deletion of betaNLS, alpha/betaNLS, or both as well as R393A and R393N mutations severely impaired NS5 nuclear import and consequently conferred NS5 degradation. The R393A and R393N mutations also ablated viral RNA replication and virus production. Treatment of ZIKV-infected cells with importin alpha/beta-NS5 interaction inhibitors ivermectin or 4-HPR resulted in a rapid degradation of NS5 similar to the R393 A/N mutations. Collectively, these findings suggest that NS5 nuclear accumulation protects NS5 from cytoplasmic degradation and therefore is required for viral RNA replication.
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Sequence Data
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-
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