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Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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 <jats:italic>via<\/jats:italic> intensive characterization of HBV s gene in both chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A total of 73 HBsAg+\/HBsAb+ patients (CHB = 36, HCC = 37) and 96 HBsAg+\/HBsAb\u2212 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2212 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 &amp;lt; 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.775461","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T02:37:23Z","timestamp":1638326243000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["The Impact of HBV Quasispecies Features on Immune Status in HBsAg+\/HBsAb+ Patients With HBV Genotype C Using Next-Generation 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