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Basic Characteristics of Mutations
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Mutation Site
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T51K |
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Mutation Site Sentence
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Sequencing of resistant viruses revealed a single T51K substitution in the domain I/II hinge region of the viral envelope protein. |
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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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E |
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Standardized Encoding Gene
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Envelope
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Genotype/Subtype
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DENV-1 |
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Viral Reference
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U88535
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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
|
HM14c10 |
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Location
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- |
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Literature Information
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PMID
|
22771779
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Title
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Resistance analysis of an antibody that selectively inhibits dengue virus serotype-1
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Author
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Zou G,Kukkaro P,Lok SM,Ng JK,Tan GK,Hanson BJ,Alonso S,MacAry PA,Shi PY
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Journal
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Antiviral research
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Journal Info
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2012 Sep;95(3):216-23
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Abstract
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The four serotypes of dengue virus (DENV) are the causative agents of the most prevalent mosquito-borne viral disease in human. No clinically approved antiviral therapy is currently available. Therapeutic antibodies represent a viable approach for potential treatment of DENV infection. We recently isolated a human monoclonal antibody (HM14c10) that selectively neutralizes DENV serotype 1 (DENV-1), but not serotypes 2, 3, and 4. Here we report the resistance profile of DENV-1 against HM14c10 in cell culture. Escape mutant viruses readily emerged by culturing wild-type DENV-1 in the presence of the HM14c10 antibody. Sequencing of resistant viruses revealed a single T51K substitution in the domain I/II hinge region of the viral envelope protein. Residue T51 is located within the HM14c10 epitope and is highly conserved among various DENV-1 isolates. Recombinant DENV-1 containing the T51K mutation could not be neutralized by HM14c10 in vitro or in vivo. Biochemical assay revealed that the T51K mutation completely abolished the antibody binding to the DENV-1 virion. Collectively, the results demonstrate that a single amino acid change in DENV envelope protein can confer resistance to a potent antibody through abolishing the antibody-virus interaction.
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Sequence Data
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-
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