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Basic Characteristics of Mutations
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Mutation Site
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N51T |
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Mutation Site Sentence
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Specifically, downregulation function was increased modestly for N51T, I114V, and S163C mutants, each of which displayed ~5% higher activity compared with parental Nef;whereas downregulation was impaired for C55S, K94E, H116N, V148L, and S163R mutants, each of which displayed 5%-50% lower activity compared with parental Nef. |
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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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Nef |
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Standardized Encoding Gene
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Nef
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Genotype/Subtype
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HIV-1 B |
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Viral Reference
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K03455.1
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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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Y |
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Treatment
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- |
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Location
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Boston (USA) |
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Literature Information
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PMID
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31693887
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Title
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Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity
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Author
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Jin SW,Alsahafi N,Kuang XT,Swann SA,Toyoda M,Gottlinger H,Walker BD,Ueno T,Finzi A,Brumme ZL,Brockman MA
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Journal
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Cell reports
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Journal Info
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2019 Nov 5;29(6):1449-1457
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Abstract
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HIV-1 Nef enhances virion infectivity by counteracting host restriction factor SERINC5; however, the impact of natural Nef polymorphisms on this function is largely unknown. We characterize SERINC5 downregulation activity of 91 primary HIV-1 subtype B nef alleles, including isolates from 45 elite controllers and 46 chronic progressors. Controller-derived Nef clones display lower ability to downregulate SERINC5 (median 80% activity) compared with progressor-derived clones (median 96% activity) (p = 0.0005). We identify 18 Nef polymorphisms associated with differential function, including two CTL escape mutations that contribute to lower SERINC5 downregulation: K94E, driven by HLA-B( *)08, and H116N, driven by the protective allele HLA-B( *)57. HIV-1 strains encoding Nef K94E and/or H116N display lower infectivity and replication capacity in the presence of SERINC5. Our results demonstrate that natural polymorphisms in HIV-1 Nef can impair its ability to internalize SERINC5, indicating that variation in this recently described function may contribute to differences in viral pathogenesis.
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Sequence Data
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JX171199-JX171243;JX440926-JX440971
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