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Basic Characteristics of Mutations
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Mutation Site
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L262V |
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Mutation Site Sentence
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Among the high-level variations found in ICC, six were located in the E1/E2 genes, and all of them were non-synonymous substitutions (Q142K, M207I, and L262V for E1; D153Y, R302T, and T357A for E2). |
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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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E1 |
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Standardized Encoding Gene
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E1
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Genotype/Subtype
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HPV16 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Uterine Cervical Neoplasms
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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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Japan |
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Literature Information
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PMID
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33324377
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Title
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High Levels of Within-Host Variations of Human Papillomavirus 16 E1/E2 Genes in Invasive Cervical Cancer
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Author
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Hirose Y,Yamaguchi-Naka M,Onuki M,Tenjimbayashi Y,Tasaka N,Satoh T,Tanaka K,Iwata T,Sekizawa A,Matsumoto K,Kukimoto I
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Journal
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Frontiers in microbiology
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Journal Info
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2020 Nov 24;11:596334
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Abstract
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Human papillomavirus type 16 (HPV16) is the most common HPV genotype found in invasive cervical cancer (ICC). Recent comprehensive genomics studies of HPV16 have revealed that a large number of minor nucleotide variations in the viral genome are present in each infected woman; however, it remains unclear whether such within-host variations of HPV16 are linked to cervical carcinogenesis. Here, by employing next-generation sequencing approaches, we explored the mutational profiles of the HPV16 genome within individual clinical specimens from ICC (n = 31) and normal cervix (n = 21) in greater detail. A total of 367 minor nucleotide variations (167 from ICC and 200 from the normal cervix) were detected throughout the viral genome in both groups, while nucleotide variations at high frequencies (>10% abundance in relative read counts in a single sample) were more prevalent in ICC (10 in ICC versus 1 in normal). Among the high-level variations found in ICC, six were located in the E1/E2 genes, and all of them were non-synonymous substitutions (Q142K, M207I, and L262V for E1; D153Y, R302T, and T357A for E2). In vitro functional analyses of these E1/E2 variants revealed that E1/M207I, E2/D153Y, and E2/R302T had reduced abilities to support viral replication, and that E2/D153Y and E2/R302T failed to suppress the viral early promoter. These results imply that some within-host variations of E1/E2 present at high levels in ICC may be positively selected for and contribute to cervical cancer development through dysfunction or de-stabilization of viral replication/transcription proteins.
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Sequence Data
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DRA009226
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