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    • There are five main research

    2021-09-16

    There are five main research findings regarding possible mechanisms of low-level HBsAg expression: Most of these findings are related to the use of antiviral therapy, which results in pre-S/S gene mutations, the development of occult hepatitis, the use of immunosuppressants or S gene methylation, but few studies have investigated the sequence characteristics of the HBV S gene in the low-level HBsAg ASC population. Therefore, in this study, we compared the S gene sequences of HBV infection cases of ASCs with low-level HBsAg expression with the established genotype B and C reference sequences and HBV-infected cases with high-level HBsAg. The results showed that the amino 91 5 mutation rate and the number of mutation sites in the SHBs protein in the low-level HBsAg group, which primarily consisted of genotype B, were higher than those in the high-level HBsAg group (P < 0.05). The mutation sites were mostly distributed on both sides of the MHR (amino acid residues 40–49 and 198–220) (Fig. 3B). The distribution of these mutation sites was significantly different from the distribution of the mutation sites in the occult hepatitis, CHB and HBV infection with the coexistence of HBsAg and anti-HBs; in that case, most of the mutation sites are found inside the MHR [51], [52], [53]. We further analysed the amino acid mutation sites of SHBs in the high- and low-level HBsAg groups of ASCs from the perspectives of single-site mutations and multi-site co-mutations. The distribution of significant amino acid mutations found in the different genotypes in the two groups is shown in Table 5. In genotype B, hotspot (including 8 single-site mutations and 1 two-site co-mutation) and non-hotspot mutations (including 1 single-site mutation and 3 two-site co-mutations) were found in the low-level group, and 2 single-site mutations and 2 two-site co-mutations found in the high-level HBsAg group were hotspot mutations. In genotype C, hotspot mutations including 5 single-site mutations (T5A, A45T, T47A/K, Q101R, I126S/T) and 1 single-site mutation (N3S) were found in the low- and high-level HBsAg groups, respectively. In genotype B, the mutation frequencies of 2 single-site mutations, 2 two-site co-mutations in the high -level group were higher than in the low-level group, and the others in the low-level group were higher than those in the high-level group. In genotype C, the mutation frequency of 1 single-site mutation in the high-level group was higher than that in the low-level group, and the others in the low-level group were higher than those in the high-level group. HBsAg expression in HBV may be a bi-directional regulation of gene mutation. In other words, it can increase the expression level of HBsAg by the gene mutation and conversely reduce the expression level. However, whether these mutations determine the key sites of low expression of HBsAg requires further proof by the establishment of the model for expression in vitro.
    Conclusion In summary, a large-scale study of 1308 ASC cases grouped based on HBsAg level (10 IU/mL) was performed. Based on previous research results, the clinical features of cases with low-level HBsAg were analysed in detail. After establishing an HBV S gene reference sequence for ASC cases with a high expression of HBsAg in Eastern China, a comparative analysis of the HBV S gene sequence in patients with low-level HBsAg expression was performed. The results of this analysis suggest a possible mechanism for low-level HBsAg expression at the 91 5 molecular level; the process of HBV immune clearance by the host appears to trigger significant mutations (including co-mutations) on both sides of the MHR, which may be one cause of low HBsAg expression.
    Funding
    Disclosure of interest
    Acknowledgements
    Introduction RNA interference (RNAi) is a conserved mechanism against exogenous nucleic acid and transposon transcripts in organisms ranging from nematodes to humans, which is mediated by short double-stranded (ds) RNAs usually 21 or 22 nucleotides in length (Elbashir et al., 2001). The great potential of RNAi is the specific repression of the expression of disease-causing genes.