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

Abstract

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.

Case report: An occult hepatitis B virus infection reactivation in an HIV/HCV coinfected patient during an immune reconstitution inflammatory syndrome

“…Firstly, the failure of immune surveillance and the following immune reconstitution-induced inflammatory syndrome (IRIS) after ART reintroduction. Secondly, reinfection cannot be excluded but is rather unlikely because immunity to HBV is developed against several epitopes and should be protective against other possible HBV subtype infections (Wang et al, 2021).…”

“…An impaired HBV-specific CD4 cell response has been associated with HBV persistence even in presence of HBV-specific cells in HBV/HCV co-infected patients (Urbani et al, 2005). Wang et al described a positive relation between frequency of HBV-specific CD4 cells (mainly HBV core-specific TNF-a producing CD4 cells), hepatitis B flares and liver damage, indicating robust on-going T cell responses in patients with HBV chronic infection (Wang et al, 2021). A further differentiation of those HBV-specific TNF-a producing CD4 cells into IFN-g producing CD4 cells favors HBV viral clearance.…”

The high prevalence of occult hepatitis B infections among the partners of chronically infected HBV blood donors emphasizes the potential residual risk to blood safety

“…In contrast, a V200‐vaccinee with OBI was infected by the I126S HBV vaccine escape strain with a relatively high viral load of 15 100 IU/mL through sexual or close contact between couple. The I126S mutation may alter the conformational structure of this region, thereby modifying the antigenicity or immunogenicity of HBsAg and resulting in immune escape 34 . All HBsAg carrier donors are asymptomatic and unaware of their infection; otherwise, they are excluded via a questionnaire before donation.…”

Deep Sequencing of HPV16 E6 Region Reveals Unique Mutation Pattern of HPV16 and Predicts Cervical Cancer

“…The complexity of each aa position in the E6 region was calculated based on mutation features established by our previous research ( 23 , 24 ). Mutations were identified and analyzed using R scripts.…”

“…Previously, we have proposed a method to predict hepatocellular carcinoma using machine learning models based on HBV rt/s gene pattern features derived from NGS data ( 23 , 24 ). In this study, we aimed to detect the E6 region of HPV16 positive patients by NGS to obtain the amino acid (aa) mutation features for individual HSIL prediction.…”