Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China.
Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Guangdong, China.
J Med Virol. 2017 Jan;89(1):139-145. doi: 10.1002/jmv.24609. Epub 2016 Jul 4.
This study aimed to reveal characteristics and clinical relevance of HBV intergenotypic recombinants. Serum samples of 516 patients from Northern China were collected, including 131 with acute hepatitis B (AHB), 239 with chronic hepatitis B (CHB), and 146 with acute-on-chronic liver failure (ACLF). Full-length HBV genomes were sequenced and HBV genotypes were analyzed. Genotypes C, B, D, and intergenotypic recombinants were detected in 71.12% (367/516), 19.96% (103/516), 0.78% (4/516), and 8.14% (42/516) of the patients. The latter comprised 21 with AHB, 10 with CHB, and 11 with ACLF; and the occupations of intergenotypic recombinants in AHB, CHB, and ACLF groups were 16.03%, 4.18%, and 7.53% (P < 0.01), respectively. HBV B/C and C/D hybrids accounted for 85.71% (36/42) and 14.29% (6/42) of the intergenotypic recombinants. In AHB and CHB groups, serum HBV DNA levels were significantly lower in patients with intergenotypic recombinants than those without intergenotypic recombinants. Difference in basal core promoter A1762T/G1764A mutations and precore G1896A mutation incidences was not significant between B/C recombinant and genotypes B or C virus, although the significance was there between genotypes B and C viruses. Clonal sequence analysis showed that intergenotypic recombinant viral strains existed in single or in concomitance with other genotype virus. Phenotypic analysis showed that viral replication capacity was similar between recombinant and non-recombinant strains in tested samples. Taken together, the occurrence of intergenotypic recombinant HBV is relatively low in HBV-infected patients in Northern China, and intergenotypic recombinant HBV infection is likely favorable to induce an acute course of disease. J. Med. Virol. 89:139-145, 2017. © 2016 Wiley Periodicals, Inc.
本研究旨在揭示 HBV 基因型间重组体的特征和临床相关性。收集了来自中国北方的 516 例患者的血清样本，包括 131 例急性乙型肝炎（AHB）、239 例慢性乙型肝炎（CHB）和 146 例慢加急性肝衰竭（ACLF）患者。对全长 HBV 基因组进行测序并分析 HBV 基因型。在中国北方的 HBV 感染患者中，基因型 C、B、D 和基因型间重组体的检出率分别为 71.12%（367/516）、19.96%（103/516）、0.78%（4/516）和 8.14%（42/516）。后者包括 21 例 AHB、10 例 CHB 和 11 例 ACLF；HBV 基因型间重组体在 AHB、CHB 和 ACLF 患者中的职业分布分别为 16.03%、4.18%和 7.53%（P<0.01）。HBV B/C 和 C/D 杂种分别占基因型间重组体的 85.71%（36/42）和 14.29%（6/42）。在 AHB 和 CHB 组中，基因型间重组体患者血清 HBV DNA 水平明显低于无基因型间重组体患者。尽管基因型 B 和 C 病毒之间存在显著差异，但在 B/C 重组病毒与基因型 B 或 C 病毒之间，B 核心启动子 A1762T/G1764A 突变和前 C 区 G1896A 突变的发生率无显著差异。克隆序列分析表明，基因型间重组病毒株存在于单个病毒株或与其他基因型病毒株同时存在。表型分析表明，在检测样本中，重组和非重组病毒株的病毒复制能力相似。总之，在中国北方 HBV 感染患者中，HBV 基因型间重组体的发生率相对较低，基因型间重组 HBV 感染可能有利于诱导疾病的急性过程。J. Med. Virol. 89:139-145, 2017. © 2016 Wiley Periodicals, Inc.
