Yang Zhi-Tao, Huang Su-Yuan, Chen Li, Liu Feng, Cai Xiao-Hui, Guo Yang-Fan, Wang Ming-Jie, Han Yue, Yu De-Min, Jiang Jie-Hong, Zhang Dong-Hua, Gong Qi-Ming, Zhang Guo-Qing, Zang Guo-Qing, Lu Zhong-Hua, Huang Li-Hua, Zhang Xin-Xin
Emergency Department, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
J Clin Microbiol. 2015 Jul;53(7):2203-14. doi: 10.1128/JCM.00068-15. Epub 2015 Apr 29.
Hepatitis B virus (HBV) infection results in different clinical presentation due to different levels of immune response. Our study aimed to characterize HBV full-length genome quasispecies (QS) in patients with different phases of infection to better understand its pathogenesis. Forty treatment-naive HBV-infected patients were enrolled, including 10 cases of acute hepatitis B (AHB), 9 cases of immunotolerant (IT) HBV carriers, 11 cases of chronic hepatitis B (CHB), and 10 cases of acute-on-chronic liver failure (ACLF). The present study was conducted by clone-based sequencing. QS heterogeneity within each open reading frame was calculated. The mutation frequency index (MFI) and amino acid variations within the large HBsAg, HBcAg, and HBxAg regions were analyzed based on the different infection phases. In total, 606 HBV full-length sequences were obtained. HBV QS had higher heterogeneity in ACLF and CHB than that in IT among chronically infected individuals. AHB patients had the lower QS heterogeneity at onset than those with chronic infection. ACLF patients had the highest frequency of mutations in the core promoter and precore region. A triple mutation (A1762T/G1764A/G1896A) was observed more frequently in genotype C than in genotype B. The MFI indicated that specific peptides of the studied regions had more frequent mutations in ACLF. Furthermore, several amino acid variations, known as T- and B-cell epitopes, were potentially associated with the immunoactive phase of infection. More HBV genome mutations and deletions were observed in patients with more severe diseases, particularly in specific regions of the core and preS regions, the clinical significance and mechanism of which need to be further investigated.
由于免疫反应水平不同，乙型肝炎病毒（HBV）感染会导致不同的临床表现。我们的研究旨在对不同感染阶段患者的HBV全长基因组准种（QS）进行特征分析，以更好地了解其发病机制。纳入了40例未经治疗的HBV感染患者，包括10例急性乙型肝炎（AHB）、9例免疫耐受（IT）HBV携带者、11例慢性乙型肝炎（CHB）和10例慢加急性肝衰竭（ACLF）。本研究采用基于克隆的测序方法。计算每个开放阅读框内的QS异质性。基于不同感染阶段分析了大HBsAg、HBcAg和HBxAg区域内的突变频率指数（MFI）和氨基酸变异。共获得606条HBV全长序列。在慢性感染个体中，ACLF和CHB患者的HBV QS异质性高于IT患者。AHB患者发病时的QS异质性低于慢性感染患者。ACLF患者核心启动子和前核心区域的突变频率最高。三重突变（A1762T/G1764A/G1896A）在C基因型中比在B基因型中更频繁地观察到。MFI表明，研究区域的特定肽段在ACLF中具有更频繁的突变。此外，一些已知为T细胞和B细胞表位的氨基酸变异可能与感染的免疫活性阶段相关。在病情更严重的患者中观察到更多的HBV基因组突变和缺失，特别是在核心和前S区域的特定区域，其临床意义和机制有待进一步研究。
