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Basic Characteristics of Mutations
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Mutation Site
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D325E |
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Mutation Site Sentence
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We validated the differ_x0002_ential effects of mutations to site 325 by testing three different mutants at this site in TZM-bl neutralization assays: the maximal effect for 10-1074 was a 27-fold increase in IC50, whereas the maximal effect for PGT121 was just a 1.7-fold increase(D325E; Figure S3). |
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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 |
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Viral Reference
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HXB2
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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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Y |
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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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30709739
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Title
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An Antigenic Atlas of HIV-1 Escape from Broadly Neutralizing Antibodies Distinguishes Functional and Structural Epitopes
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Author
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Dingens AS,Arenz D,Weight H,Overbaugh J,Bloom JD
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Journal
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Immunity
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Journal Info
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2019 Feb 19;50(2):520-532
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Abstract
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Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus's envelope (Env) protein and are themselves promising immunotherapies. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. Although structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here, we mapped how all possible single amino acid mutations in Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites near, but not in direct contact with, the antibody. The Env mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs's independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.
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Sequence Data
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-
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