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Basic Characteristics of Mutations
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Mutation Site
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D10A |
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Mutation Site Sentence
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The macro domain D10A mutant also resulted in a dramatic reduction in virus infectivity, consistent with the notion that the ability of the macro domain to inhibit NF-kappaB activation plays a role in the virus lifecycle. |
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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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nsP3 |
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Standardized Encoding Gene
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nsP3
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Genotype/Subtype
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ECSA |
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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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40006946
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Title
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The Chikungunya Virus nsP3 Macro Domain Inhibits Activation of the NF-kappaB Pathway
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Author
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Roberts GC,Stonehouse NJ,Harris M
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Journal
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Viruses
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Journal Info
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2025 Jan 29;17(2):191
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Abstract
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The role of the chikungunya virus (CHIKV) non-structural protein 3 (nsP3) in the virus lifecycle is poorly understood. The protein comprises three domains. At the N-terminus is a macro domain, biochemically characterised to bind both RNA and ADP-ribose and to possess ADP-ribosyl hydrolase activity-an enzymatic activity that removes ADP-ribose from mono-ADP-ribosylated proteins. As ADP-ribosylation is important in the signalling pathway, leading to activation of the transcription factor NF-kappaB, we sought to determine whether the macro domain might perturb NF-kappaB signalling. We first showed that CHIKV infection did not induce NF-kappaB activation and could not block exogenous activation of the pathway via TNFalpha, although TNFalpha treatment did result in a modest reduction in virus titre. In contrast, ectopic expression of nsP3 was able to inhibit both basal and TNFalpha-mediated NF-kappaB activation, and this was dependent on the macro domain, as a mutation previously shown to disrupt ADP-ribose binding and hydrolase activity (D10A) eliminated the ability to inhibit NF-kappaB activation. The macro domain D10A mutant also resulted in a dramatic reduction in virus infectivity, consistent with the notion that the ability of the macro domain to inhibit NF-kappaB activation plays a role in the virus lifecycle.
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Sequence Data
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-
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