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Basic Characteristics of Mutations
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Mutation Site
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M133T |
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Mutation Site Sentence
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Sixteen differential high frequencies of missense mutations were identified (p < 0.05), including P46L, P62L, L77R, Y100S, Q101H, M103L, L104F, T118P, T125P, I126S/T, T131N, M133T/S, G145R, and I195M. |
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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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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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C |
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Viral Reference
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X04615;AY123041;AB014381
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Functional Impact and Mechanisms
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Disease
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Hepatitis B, Chronic
Carcinoma, Hepatocellular
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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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Y |
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Treatment
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- |
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Location
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China |
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Literature Information
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PMID
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34899733
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Title
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The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing
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Author
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Wang Y,Xiao X,Chen S,Huang C,Zhou J,Dai E,Li Y,Liu L,Huang X,Gao Z,Wu C,Fang M,Gao C
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Journal
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Frontiers in immunology
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Journal Info
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2021 Nov 25;12:775461
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Abstract
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BACKGROUND: This study aimed to explore the molecular mechanism of the coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) serological pattern via intensive characterization of HBV s gene in both chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients. METHOD: A total of 73 HBsAg+/HBsAb+ patients (CHB = 36, HCC = 37) and 96 HBsAg+/HBsAb- patients (CHB = 47, HCC = 49) were enrolled from 13 medical centers in China. The sequence features were elaborated based on the combination of next-generation sequencing (NGS) and multidimensional bioinformatics analysis. RESULTS: The 16 high-frequency missense mutations, changes of stop codon mutation, clustering, and random forest models based on quasispecies features demonstrated the significant discrepancy power between HBsAg+/HBsAb+ and HBsAg+/HBsAb- in CHB and HCC, respectively. The immunogenicity for cytotoxic T lymphocyte (CTL) epitope Se and antigenicity for the major hydrophilic region (MHR) were both reduced in HBsAg+/HBsAb+ patients (CTL Se: p < 0.0001; MHR: p = 0.0216). Different mutation patterns were observed between HBsAg+/HBsAb+ patients with CHB and with HCC. Especially, mutations in antigenic epitopes, such as I126S in CHB and I126T in HCC, could impact the conformational structure and alter the antigenicity/immunogenicity of HBsAg. CONCLUSION: Based on NGS and bioinformatics analysis, this study indicates for the first time that point mutations and quasispecies diversities of HBV s gene could alter the MHR antigenicity and CTL Se immunogenicity and could contribute to the concurrent HBsAg+/HBsAb+ with different features in HCC and CHB. Our findings might renew the understanding of this special serological profile and benefit the clinical management in HBV-related diseases.
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Sequence Data
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-
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