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Basic Characteristics of Mutations
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Mutation Site
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W325C |
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Mutation Site Sentence
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In addition to T353P, other mutations in this sample may lead to changes in the secondary structure, including W325C at G2 beta-sheet, G367P at beta-I sheet, T389S at alpha-2 helix, L441I at a beta-turn, Q461P and F462Y near alpha-5 helix. |
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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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L1 |
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Standardized Encoding Gene
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L1
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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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Squamous Intraepithelial Lesions
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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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- |
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Literature Information
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PMID
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31231420
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Title
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Abundance of HPV L1 Intra-Genotype Variants With Capsid Epitopic Modifications Found Within Low- and High-Grade Pap Smears With Potential Implications for Vaccinology
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Author
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Shen-Gunther J,Cai H,Zhang H,Wang Y
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Journal
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Frontiers in genetics
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Journal Info
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2019 May 24;10:489
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Abstract
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Background: The aim of this study was to explore the Human Papillomavirus (HPV) genotype composition and intra-genotype variants within individual samples of low- and high-grade cervical cytology by deep sequencing. Clinical, cytological, sequencing, and functional/structural data were forged into an integrated variant profiling pipeline for the detection of potentially vaccine-resistant genotypes or variants. Methods: Low- and high-grade intraepithelial lesion (LSIL and HSIL) cytology samples with +HPV were subjected to amplicon (L1 gene fragment) sequencing by dideoxy (Sanger) and deep methods. Taxonomic, abundance, diversity, and phylogenetic analyses were conducted to determine HPV genotypes/sub-lineages, relative abundance, species diversity and phylogenetic distances within and between samples. Variant detection and functional analysis of translated L1 amino acid sequences determined structural variations of interest. Results: Pure and mixed HPV infections were common among LSIL (n = 6) and HSIL (n = 6) samples. Taxonomic profiling revealed loss of species richness and gain of dominance by carcinogenic genotypes in HSIL samples. Phylogenetic analysis showed excellent correlation between HPV-type specific genetic distances and carcinogenic potential. For combined LSIL/HSIL samples (n = 12), 11 HPV genotypes and 417 mutations were detected: 375 single-nucleotide variants (SNV), 29 insertion/deletion (indel), 12 multi-nucleotide variants (MNV), and 1 replacement variant. The proportion of nonsynonymous mutations was lower for HSIL (0.38) than for LSIL samples (0.51) (p < 0.05). HPV variant analysis pinpointed nucleotide-level mutations and amino acid-level structural modifications. Conclusion: HPV L1 intra-host and intra-genotype variants are abundant in LSIL and HSIL samples with potential functional/structural consequences. An integrated multi-omics approach to variant analysis may provide a sensitive and practical means of detecting changes in HPV evolution and dynamics within individuals or populations.
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Sequence Data
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-
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