The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing

The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing

BackgroundThis 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) patie...

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Autores principales: Ying Wang, Xiao Xiao, Shipeng Chen, Chenjun Huang, Jun Zhou, Erhei Dai, Ya Li, Lijuan Liu, Xianzhang Huang, Zhiyuan Gao, Chuanyong Wu, Meng Fang, Chunfang Gao
Formato: article
Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
Materias:
next-generation sequencing (NGS)
hepatitis B virus (HBV)
quasispecies
hepatitis B surface antigen (HBsAg)
hepatitis B surface antibody (HBsAb)
Immunologic diseases. Allergy
RC581-607
Acceso en línea:https://doaj.org/article/7ce3ed3fae514a03890c24200da82fb8
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spelling oai:doaj.org-article:7ce3ed3fae514a03890c24200da82fb82021-12-01T02:35:44ZThe Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing1664-322410.3389/fimmu.2021.775461https://doaj.org/article/7ce3ed3fae514a03890c24200da82fb82021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.775461/fullhttps://doaj.org/toc/1664-3224BackgroundThis 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.MethodA 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.ResultsThe 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.ConclusionBased 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.Ying WangXiao XiaoXiao XiaoShipeng ChenChenjun HuangJun ZhouErhei DaiYa LiLijuan LiuXianzhang HuangZhiyuan GaoZhiyuan GaoChuanyong WuMeng FangChunfang GaoChunfang GaoFrontiers Media S.A.articlenext-generation sequencing (NGS)hepatitis B virus (HBV)quasispecieshepatitis B surface antigen (HBsAg)hepatitis B surface antibody (HBsAb)Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic next-generation sequencing (NGS)
hepatitis B virus (HBV)
quasispecies
hepatitis B surface antigen (HBsAg)
hepatitis B surface antibody (HBsAb)
Immunologic diseases. Allergy
RC581-607
spellingShingle next-generation sequencing (NGS)
hepatitis B virus (HBV)
quasispecies
hepatitis B surface antigen (HBsAg)
hepatitis B surface antibody (HBsAb)
Immunologic diseases. Allergy
RC581-607
Ying Wang
Xiao Xiao
Xiao Xiao
Shipeng Chen
Chenjun Huang
Jun Zhou
Erhei Dai
Ya Li
Lijuan Liu
Xianzhang Huang
Zhiyuan Gao
Zhiyuan Gao
Chuanyong Wu
Meng Fang
Chunfang Gao
Chunfang Gao
The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing
description BackgroundThis 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.MethodA 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.ResultsThe 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.ConclusionBased 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.
format article
author Ying Wang
Xiao Xiao
Xiao Xiao
Shipeng Chen
Chenjun Huang
Jun Zhou
Erhei Dai
Ya Li
Lijuan Liu
Xianzhang Huang
Zhiyuan Gao
Zhiyuan Gao
Chuanyong Wu
Meng Fang
Chunfang Gao
Chunfang Gao
author_facet Ying Wang
Xiao Xiao
Xiao Xiao
Shipeng Chen
Chenjun Huang
Jun Zhou
Erhei Dai
Ya Li
Lijuan Liu
Xianzhang Huang
Zhiyuan Gao
Zhiyuan Gao
Chuanyong Wu
Meng Fang
Chunfang Gao
Chunfang Gao
author_sort Ying Wang
title The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing
title_short The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing
title_full The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing
title_fullStr The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing
title_full_unstemmed The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing
title_sort impact of hbv quasispecies features on immune status in hbsag+/hbsab+ patients with hbv genotype c using next-generation sequencing
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/7ce3ed3fae514a03890c24200da82fb8
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