Distinctive sequence characteristics of subgenotype A1 isolates of hepatitis B virus from South Africa
Distinctive sequence characteristics of subgenotype A1 isolates of hepatitis B virus from South Africa
复制标题
DOI：
10.1099/vir.0.19749-0
复制
发表时间：
2004-05-01
影响因子：
3.8
通讯作者：
Kew, MC
中科院分区：
文献类型：
--
作者：
Kimbi, GC;Kramvis, A;Kew, MC
对乙型肝炎病毒（HBV）的系统发育分析已将其分为A到H共8个基因型。南非的主要基因型是基因型A，它由两个亚基因型A1和A2组成。亚基因型A1（先前为A'亚组）比亚基因型A2（先前为除A'之外的A亚组）更为常见。从18名无症状病毒携带者和5名急性乙型肝炎患者体内分离出的HBV全基因组被扩增；扩增产物被克隆并测序。所有急性肝炎分离株都属于亚基因型A1，与无症状携带者的分离株相比没有明显的突变，无症状携带者的分离株分布为10个亚基因型A1、2个亚基因型A2和6个基因型D。在S基因和聚合酶基因中，先前描述的区分亚基因型A1（A'亚组）与基因型A其余部分的氨基酸残基的存在得到了证实。此外，大量测序的亚基因型A1分离株使得在其他开放阅读框中能够识别出亚基因型A1特有的额外核苷酸和氨基酸变化。特别是，在1809 - 1812位的核苷酸突变改变了前核心/核心开放阅读框的科扎克序列，以及在前核心区域的A'8，仅在亚基因型A1分离株中被发现。在亚基因型A1分离株中还发现了转录调控元件的独特序列改变。亚基因型A1的平均核苷酸差异大于亚基因型A2，这表明该亚基因型在南非黑人人群中流行的时间比亚基因型A2更长。
Phylogenetic analysis of hepatitis B virus (HBV) has led to its classification into eight genotypes, A to H The dominant genotype in South Africa is genotype A, which consists of two subgenotypes, A1 and A2. Subgenotype A1 (previously subgroup A') predominates over subgenotype A2 (previously subgroup A minus A'). The complete genome of HBV isolated from 18 asymptomatic carriers of the virus and five acute hepatitis B patients was amplified; the resulting amplicons were cloned and sequenced. All acute hepatitis isolates belonged to subgenotype A1 and had no distinguishing mutations relative to the isolates from asymptomatic carriers, which had a distribution of ten subgenotype A1, two subgenotype A2 and six genotype D. The presence of the previously described amino acid residues that distinguish subgenotype A1 (subgroup A') from the remainder of genotype A in the S and polymerase genes was confirmed, Moreover, the large number of subgenotype A1 isolates sequenced allowed identification in the other open reading frames of additional nucleotide and amino acid changes that are characteristic of subgenotype A1. In particular, nuclectide mutations at positions 1809-1812 that alter the Kozak sequence of the precore/core open reading frame, and A' 8 in the precore region, were found exclusively in subgenotype A1 isolates. Unique sequence alterations of the transcriptional regulatory elements were also found in subgenotype A1 isolates. The mean nucleotide divergence of subgenotype A1 was greater than that of sulogenotype A2, suggesting that this subgenotype has been endemic for a longer time in the South African black population than had subgenotype A2.