Analysis of S gene characteristic sequences and changes in properties of protein expression in HBV ASCs with low-level HBsAg

Abstract

ObjectiveWe detected the serum HBsAg immune complex (HBsAg-CIC) and sequenced the HBV S gene in these patients to reveal the association between sustained low-level expression of HBsAg and mutated S gene sequence characteristics, protein function changes, and HBsAg immune complex formation.MethodsA total of 204 samples were collected and divided into high-level (n = 60, HBsAg level >10 IU/ml) and low-level (n = 144, HBsAg level ≤ 10 IU/ml) HBsAg groups. The clinical and epidemiological data of the two groups were statistically compared. According to different serological patterns and genotypes, the HBsAg-CIC results of the high-level and low-level HBsAg groups were divided into different subgroups, and then the HBsAg-CIC positive rates among different subgroups were compared. We sequenced the S gene of HBV from the two groups and identified the relevant mutations in the MHR of the S gene. In addition, we compared the changes in HBsAg protein properties and functions after hot spot mutation in the MHR of the S gene.ResultsComparing the positive rates of HBsAg-CIC under different serological patterns and genotypes in the two groups, the HBsAg-CIC positive rate was higher in the low-level HBsAg group. Moreover, there was weak correlation between HBsAg-CIC and HBsAg or HBV DNA in both groups (r = 0.32, 0.27, 0.41, 0.48; P < 0.05). Sequencing of S gene in the two groups, showed that the hot-spot mutations were T126A, M133L/T/S, and F134L/T/I in MHR of S gene of genotype B, and hot-spot mutations were Q101R and I126S/T in MHR of S gene of genotype C. Additionally, the positive rate of MHR mutation in the S gene from HBsAg-CIC positive patients was higher in the low-level HBsAg group.ConclusionThe host immune process of clearing HBV seems to have multiple site mutations in MHR, which changes the physicochemical properties and functions of HBsAg and intensifies the formation of HBsAg-CIC, thus avoiding the effective recognition of HBsAg by the host and resulting in immune tolerance between the host and HBV, which may be one of the formation mechanisms of sustained low-level expression of HBsAg in the serum of HBV-infected persons.

Hepatitis B virus reactivation in hepatocellular carcinoma patients after hepatic arterial infusion chemotherapy combined with and without immunotherapy

“…HBVr can occur during immunosuppression in patients with chronic hepatitis B (anti-HBc-positive and HBsAg positive) or resolved infection (anti-HBc-positive and HBsAg negative) [ 28 , 29 ]. Liu et al [ 30 ] found that the occurrence of HBVr in HCC patients after HAIC was 11.7% (16/137) in the antiviral group and 27.3% (9/33) in the non-antiviral group.…”

Measuring HBV pregenomic RNA may be a potential biomarker to determine HBV functional cure in HIV/HBV‐co‐infected patients with HBsAg loss

“…Patients who tested negative for HBV pgRNA at the time of HBsAg loss had low baseline HBV DNA and HBsAg levels, as well as low HBV replication levels.Considering the potential association between HBV pgRNA and viral replication, this study suggests that HBsAg loss should not be the sole criterion for evaluating a functional cure in HIV/HBV coinfection. Owing to the unique immune status of HIV patients and the strong antiviral effects of ART, HBsAg in HIV/HBV-co-infected individuals may undergo mutations, making it difficult to detect or produce nonsecretory HBsAg using existing testing methods 15. HBsAg loss is not a comprehensive indicator of HBV functional cure in HIV/HBV-co-infected individuals.…”