AUTHOR=Wang Ying , Xiao Xiao , Chen Shipeng , Huang Chenjun , Zhou Jun , Dai Erhei , Li Ya , Liu Lijuan , Huang Xianzhang , Gao Zhiyuan , Wu Chuanyong , Fang Meng , Gao Chunfang TITLE=The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.775461 DOI=10.3389/fimmu.2021.775461 ISSN=1664-3224 ABSTRACT=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.