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Basic Characteristics of Mutations
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Mutation Site
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K160N |
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Mutation Site Sentence
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(Left) blots treated with IgG purified from rabbits immunized with CONEs; (Right) same blots stripped from CONE IgG and treated with anti-gp140 IgG as a positive control. Lanes: 1–2, 1086 gp120 D7 293F; lanes 3–4, C.TV1C8.2D11 gp120; lanes 5–6, CHO monomer 1086 D7 gp120 K160N; lane 7, PageRuler Plus Prestained Protein Ladder. Source data are provided as a Source Data file |
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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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Env |
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Standardized Encoding Gene
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Env
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Genotype/Subtype
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HIV-1 C |
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Viral Reference
|
HXB2 HIV-1
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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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Location
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- |
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Literature Information
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PMID
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30814513
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Title
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Rationally designed carbohydrate-occluded epitopes elicit HIV-1 Env-specific antibodies
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Author
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Zhu C,Dukhovlinova E,Council O,Ping L,Faison EM,Prabhu SS,Potter EL,Upton SL,Yin G,Fay JM,Kincer LP,Spielvogel E,Campbell SL,Benhabbour SR,Ke H,Swanstrom R,Dokholyan NV
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Journal
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Nature communications
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Journal Info
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2019 Feb 27;10(1):948
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Abstract
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An array of carbohydrates masks the HIV-1 surface protein Env, contributing to the evasion of humoral immunity. In most HIV-1 isolates 'glycan holes' occur due to natural sequence variation, potentially revealing the underlying protein surface to the immune system. Here we computationally design epitopes that mimic such surface features (carbohydrate-occluded neutralization epitopes or CONE) of Env through 'epitope transplantation', in which the target region is presented on a carrier protein scaffold with preserved structural properties. Scaffolds displaying the four CONEs are examined for structure and immunogenicity. Crystal structures of two designed proteins reflect the computational models and accurately mimic the native conformations of CONEs. The sera from rabbits immunized with several CONE immunogens display Env binding activity. Our method determines essential structural elements for targets of protective antibodies. The ability to design immunogens with high mimicry to viral proteins also makes possible the exploration of new templates for vaccine development.
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Sequence Data
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-
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|
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