Norder H, Couroucé A M, Magnius L O
Department of Virology, National Bacteriological Laboratory, Stockholm, Sweden.
Virology. 1994 Feb;198(2):489-503. doi: 10.1006/viro.1994.1060.
The genomes of six hepatitis B viral (HBV) strains were sequenced from 10 overlapping amplificates obtained by the polymerase chain reaction. Four of the strains, specifying subtypes ayw4 and adw4q-, represented on the basis of divergency within the S gene two new genomic groups identified by us. The other two strains, encoding adrq- and of Pacific origin, belonged to genomic group C. The relation of these genomes to 21 published human, 1 chimpanzee, and 4 rodent hepadnaviral genomes was analyzed by constructing a phylogenetic dendrogram. Thereby, the segregation of human HBV strains into six genomic groups was confirmed. A consistent grouping of the genomes compared was also obtained in dendrograms based on the P and S genes, although the branching order differed from that based on the entire genomes. Each of the two representatives of genomic groups E and F differed by 8.1 to 13.6% and by 12.8 to 15.5% from the genomes of the other groups and by 1.5 and 3.7% from each other. The two Pacific group C strains differed by 2.7% from each other and by 4.1 to 5.4% from other group C genomes, suggesting that they diverged early from the other group C genomes. The F strains formed the most divergent group of HBV genomes, which may be explained by their representing the original strains of the New World. Within the structural gene products, 17 and 34 amino acids unique for human HBV strains were recorded in the sequenced E and F strains, respectively. Most notable is the Ser81 to Ala81 substitution in an immunodominant region of HBcAg, and the four extra cysteine residues in HBsAg at residues 19, 183, 206, and 220, which might be engaged in additional disulphide bridges. Five residues shared by E and F strains were also unique for human HBV strains. Two of these, Leu127 and Ser140 in HBsAg, were the only substitutions that may explain the w4 reactivity shared by these HBV strains. Interestingly, the Ser140 substitution occurs in an immunodominant loop of the a determinant claimed to be important for the protective immune response to HBV vaccination.
从通过聚合酶链反应获得的10个重叠扩增片段中对6株乙型肝炎病毒（HBV）的基因组进行了测序。其中4株，分别为ayw4和adw4q-亚型，根据S基因内的差异，代表了我们鉴定出的两个新基因组群。另外两株编码adrq-且源自太平洋地区，属于基因组C群。通过构建系统发育树状图，分析了这些基因组与21个已发表的人类、1只黑猩猩和4种啮齿动物嗜肝DNA病毒基因组的关系。由此证实了人类HBV毒株可分为6个基因组群。基于P基因和S基因构建的树状图中，所比较的基因组也得到了一致的分组，尽管分支顺序与基于全基因组的不同。基因组E群和F群的两个代表毒株与其他群的基因组相比，差异分别为8.1%至13.6%和12.8%至15.5%，彼此之间差异为1.5%和3.7%。太平洋地区的两株C群毒株彼此间差异为2.7%，与其他C群基因组差异为4.1%至5.4%，这表明它们在早期就与其他C群基因组发生了分化。F群毒株构成了HBV基因组中差异最大的一组，这可能是因为它们代表了新大陆的原始毒株。在结构基因产物中，测序的E群和F群毒株中分别记录到了17个和34个人类HBV毒株特有的氨基酸。最值得注意的是HBcAg免疫显性区域中Ser81到Ala81的替换，以及HBsAg中第19、183、206和220位的四个额外半胱氨酸残基，它们可能参与形成额外的二硫键。E群和F群毒株共有的五个残基也是人类HBV毒株特有的。其中两个，HBsAg中的Leu127和Ser140，是唯一可能解释这些HBV毒株共有的w4反应性原因的替换。有趣的是，Ser140替换发生在a决定簇的一个免疫显性环中，该环被认为对HBV疫苗接种的保护性免疫反应很重要。
