Laoi Bairbre Ni, Crowley B
Department of Microbiology, St James's Hospital, Dublin, Ireland.
J Med Virol. 2008 Sep;80(9):1554-64. doi: 10.1002/jmv.21273.
Hepatitis B virus (HBV) is known to show significant genetic diversity. There are eight HBV genotypes (A-H) characterized by distinct geographical distribution. Mutations in the HBV genome, in particular precore (PC) and basal core promoter (BCP) mutations, may be important factors in the pathogenesis of disease. In this study genetic heterogeneity and phylogenetic analysis of HBV isolates from 32 naïve patients with acute HBV infection was investigated. Eleven patients presented with severe infection, while the remaining 21 had self-limiting illness. Only four isolates from patients with severe HBV infection harbored the G1896A stop codon mutation. One isolate (Irish-13), collected from a patient with acute asymptomatic infection, had a G1896A mutation and a 243 bp deletion of the polymerase gene. A triple mutation, T1753C/A1762T/G1764A was identified in only one isolate (Irish-3) associated with severe infection. The latter also had a mutation, A2339G, in the core gene, not previously reported in severe acute infection caused by genotype D. Variations within the S gene were identified in 6 isolates, including Gly145Ala, associated with vaccine immune escape, Asp144Glu, Ser143Leu and Phe134Leu, each associated with failure to detect HBsAg. Phylogenetic analysis was determined using amplicons of the S gene (678 bp) and distal-X/PC region (672 bp). Genotype A was the most common (75%), followed by genotype D (15.6%), and equal proportions of C, E, F, and H. A novel recombinant of genotypes D and E was identified in an isolate originating from West Africa. Genetic heterogeneity of HBV isolates of HBV isolates from patients with acute infection needs further study of its significance.
已知乙型肝炎病毒(HBV)具有显著的遗传多样性。有八种HBV基因型(A - H),其具有不同的地理分布特征。HBV基因组中的突变,特别是前核心(PC)和基础核心启动子(BCP)突变,可能是疾病发病机制中的重要因素。在本研究中,对32例初治急性HBV感染患者的HBV分离株进行了遗传异质性和系统发育分析。11例患者表现为严重感染,其余21例为自限性疾病。仅4例严重HBV感染患者的分离株携带G1896A终止密码子突变。从一名急性无症状感染患者分离出的一株(爱尔兰 - 13)具有G1896A突变和聚合酶基因243 bp缺失。仅在一株与严重感染相关的分离株(爱尔兰 - 3)中鉴定出三联突变T1753C/A1762T/G1764A。后者在核心基因中也有一个A2339G突变,该突变在由D基因型引起的严重急性感染中尚未见报道。在6株分离株中鉴定出S基因内的变异,包括与疫苗免疫逃逸相关的Gly145Ala、与未能检测到HBsAg相关的Asp144Glu、Ser143Leu和Phe134Leu。使用S基因(678 bp)和远端 - X/PC区域(672 bp)的扩增子进行系统发育分析。A基因型最为常见(75%),其次是D基因型(15.6%),C、E、F和H基因型比例相等。在一株源自西非的分离株中鉴定出一种新的D和E基因型重组体。急性感染患者HBV分离株的遗传异质性的意义需要进一步研究。