Laboratory of Molecular Virology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Brasil Av., 4365 Manguinhos, Rio de Janeiro 21040-360, Brazil.
Department of Social Medicine, Espírito Santo Federal University, Espírito Santo 29075-910, Brazil.
Viruses. 2022 Jun 24;14(7):1375. doi: 10.3390/v14071375.
Several hepatitis B virus (HBV)-related factors, including the viral load, genotype, and genomic mutations, have been linked to the development of liver diseases. Therefore, in this study we aimed to investigate the influence of HBV genetic variability during acute and chronic infection phases. A real-time nested PCR was used to detect HBV DNA in all samples (acute, n = 22; chronic, n = 49). All samples were sequenced for phylogenetic and mutation analyses. Genotype A, sub-genotype A1, was the most common genotype in the study population. A total of 190 mutations were found in the pre-S/S gene area and the acute profile revealed a greater number of nucleotide mutations (p < 0.05). However, both profiles contained nucleotide mutations linked to immune escape and an increased risk of hepatocellular carcinomas (acute, A7T; chronic, A7Q). Furthermore, 17 amino acid substitutions were identified in the viral polymerase region, including the drug resistance mutations lamivudine and entecavir (rtL180M), with statistically significant differences between the mutant and wild type strains. Owing to the natural occurrence of these mutations, it is important to screen for resistance mutations before beginning therapy.
一些乙型肝炎病毒(HBV)相关因素,包括病毒载量、基因型和基因组突变,与肝脏疾病的发展有关。因此,本研究旨在探讨 HBV 遗传变异在急性和慢性感染阶段的影响。使用实时嵌套 PCR 检测所有样本(急性,n=22;慢性,n=49)中的 HBV DNA。对所有样本进行测序进行系统发育和突变分析。在研究人群中,最常见的基因型是 A 型,亚基因型 A1。在 Pre-S/S 基因区域发现了总共 190 个突变,急性组显示出更多的核苷酸突变(p<0.05)。然而,这两种模式都包含与免疫逃逸和肝细胞癌风险增加相关的核苷酸突变(急性,A7T;慢性,A7Q)。此外,在病毒聚合酶区域发现了 17 个氨基酸取代,包括拉米夫定和恩替卡韦的耐药突变(rtL180M),突变株和野生型株之间存在统计学差异。由于这些突变的自然发生,在开始治疗之前,筛选耐药突变非常重要。