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Basic Characteristics of Mutations
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Mutation Site
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C7531T |
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Mutation Site Sentence
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Three of those variations, T7365C, C7531T and T7791C are not found in other B-lineage LCRs and may therefore account for the higher transcriptional activity of LCR10, as tested below. |
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Mutation Level
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Nucleotide level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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LCR |
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Standardized Encoding Gene
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|
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Genotype/Subtype
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HPV33 |
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Viral Reference
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M12732.1
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Functional Impact and Mechanisms
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Disease
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-
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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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- |
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Literature Information
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PMID
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30911096
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Title
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Characterization of an HPV33 natural variant with enhanced transcriptional activity suggests a role for C/EBPbeta in the regulation of the viral early promoter
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Author
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Alvarez J,Gagnon D,Coutlee F,Archambault J
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Journal
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Scientific reports
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Journal Info
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2019 Mar 25;9(1):5113
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Abstract
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The Long Control Region (LCR) of the human papillomavirus (HPV) genome encompasses the early promoter (EP) that drives expression of the viral oncogenes in infected cells and HPV-associated cancers. Here, we report on a natural variant of HPV33 that displays higher EP activity than the prototype in transfected C33A and HeLa cervical carcinoma cells, and in the osteosarcoma U2OS cell line which supports replication of HPV episomes. This increased promoter activity was ascribed to a single nucleotide variation in the LCR, T7791C, in a putative binding site for the transcription factor C/EBPbeta. T7791C abrogated binding of recombinant C/EBPbeta to this site in vitro and stimulated the EP in vivo, suggesting that it abrogates a negatively-acting regulatory element. A second C/EBPbeta binding site was identified in vitro that activated the EP in vivo and whose function and location in the epithelial-specific enhancer is shown to be conserved in the highly prevalent HPV18. These results suggest that C/EBPbeta is both an activator and a repressor of the HPV33 EP, acting via two distinct binding sites. Prediction of C/EBPbeta sites in the LCR of 186 HPV types suggests that C/EBPbeta regulation of the EP is common among high-risk viruses from the alpha genus.
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Sequence Data
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-
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