Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgān, Iran.
Virus Genes. 2023 Oct;59(5):662-669. doi: 10.1007/s11262-023-02012-z. Epub 2023 Jun 12.
Failure to neutralize HBsAg and subsequent escape from the host immune system may be caused by HBsAg mutations, particularly in the "a" determinant, which alters the antigenicity of the protein. The purpose of this study was to examine the frequency of S gene mutations in three generations of HBV cases in northeastern Iran. In this study, 90 patients with chronic HBV were assigned to three groups according to the inclusion criteria. The plasma were utilized to extract viral DNA, and the PCR was applied. Direct sequencing and alignment were performed on the S gene, using reference sequence. The results indicated that all HBV genomes were categorized as the genotype D/ayw2. Among 79 point mutations detected, 36.8% were silent, and 56.2% were missense. In the S region, mutations were observed in 88.9% of CHB subjects studied. In the three-generation group, 21.5% of mutations were in the "a" determinant, and 2.6%, 19.5%, and 87.0% of these mutations were observed in antigenic epitopes of CTLs, CD, and B cells, respectively. In addition, 56.7% of mutations occurred at Major Hydrophilic Region. S143L and G145R mutations which the most prevalent in the three-generation (36.7%, 20%), and two-generation (42.5%, 20%) groups, related to the failure of HBsAg detection, vaccine, and immunotherapy escape. The findings showed that most of the mutations were concentrated in the B cell epitope. Most CHB cases from the three-generation, especially grandmothers, had HBV S gene mutations and subsequent amino acid mutations, suggesting that these mutations may be critical for pathogenesis and vaccine evasion.
未能中和 HBsAg 并随后逃避宿主免疫系统可能是由 HBsAg 突变引起的，特别是在“a”决定簇中，这会改变蛋白质的抗原性。本研究旨在检查伊朗东北部三代乙型肝炎病毒（HBV）病例中 S 基因突变的频率。在这项研究中，根据纳入标准将 90 名慢性 HBV 患者分为三组。利用血浆提取病毒 DNA，采用 PCR 法。使用参考序列对 S 基因进行直接测序和比对。结果表明，所有 HBV 基因组均归类为基因型 D/ayw2。在检测到的 79 个点突变中，36.8%为沉默突变，56.2%为错义突变。在 S 区，88.9%的 CHB 研究对象中观察到突变。在三代组中，21.5%的突变发生在“a”决定簇中，分别在 CTL、CD 和 B 细胞的抗原表位中观察到 2.6%、19.5%和 87.0%的这些突变。此外，56.7%的突变发生在主要亲水区。S143L 和 G145R 突变在三代（36.7%，20%）和二代（42.5%，20%）组中最为常见，与 HBsAg 检测失败、疫苗和免疫治疗逃逸有关。研究结果表明，大多数突变集中在 B 细胞表位。三代中大多数 CHB 病例，特别是祖母，均发生 HBV S 基因突变和随后的氨基酸突变，表明这些突变可能对发病机制和疫苗逃逸至关重要。
