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Basic Characteristics of Mutations
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Mutation Site
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R45K |
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Mutation Site Sentence
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In order to abrogate IkappaB stabilization and NF-kappaB inhibition downstream of tetherin, a previously described cytoplasmic arginine residue within Vpu was mutated to lysine (R45K in subtype B, R50K in subtype C). |
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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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Vpu |
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Standardized Encoding Gene
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Vpu
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Genotype/Subtype
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HIV-1 B |
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Viral Reference
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"CH293, CH077, and STCO1"
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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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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Germany |
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Literature Information
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PMID
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30717826
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Title
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HIV-1 Vpu is a potent transcriptional suppressor of NF-kappaB-elicited antiviral immune responses
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Author
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Langer S,Hammer C,Hopfensperger K,Klein L,Hotter D,De Jesus PD,Herbert KM,Pache L,Smith N,van der Merwe JA,Chanda SK,Fellay J,Kirchhoff F,Sauter D
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Journal
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eLife
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Journal Info
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2019 Feb 5;8:e41930
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Abstract
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Many viral pathogens target innate sensing cascades and/or cellular transcription factors to suppress antiviral immune responses. Here, we show that the accessory viral protein U (Vpu) of HIV-1 exerts broad immunosuppressive effects by inhibiting activation of the transcription factor NF-kappaB. Global transcriptional profiling of infected CD4 +T cells revealed that vpu-deficient HIV-1 strains induce substantially stronger immune responses than the respective wild type viruses. Gene set enrichment analyses and cytokine arrays showed that Vpu suppresses the expression of NF-kappaB targets including interferons and restriction factors. Mutational analyses demonstrated that this immunosuppressive activity of Vpu is independent of its ability to counteract the restriction factor and innate sensor tetherin. However, Vpu-mediated inhibition of immune activation required an arginine residue in the cytoplasmic domain that is critical for blocking NF-kappaB signaling downstream of tetherin. In summary, our findings demonstrate that HIV-1 Vpu potently suppresses NF-kappaB-elicited antiviral immune responses at the transcriptional level.
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Sequence Data
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GSE117655
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