The complete nucleotide sequence of a pre-core mutant of hepatitis B virus implicated in fulminant hepatitis and its biological characterization in chimpanzees.
The complete nucleotide sequence of a pre-core mutant of hepatitis B virus implicated in fulminant hepatitis and its biological characterization in chimpanzees.
复制标题
与暴发性肝炎有关的乙型肝炎病毒前核心突变体的完整核苷酸序列及其在黑猩猩中的生物学特征。
DOI：
10.1006/viro.1993.1257
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发表时间：
1993
期刊：
影响因子：
3.7
通讯作者：
Purcell,RH
中科院分区：
文献类型：
--
作者：
Ogata,N;Miller,RH;Ishak,KG;Purcell,RH
B型肝炎病毒（HBV）在病毒基因组的前核心区域内具有符合读框的终止密码子，导致两个个体发生暴发性肝炎。从一名慢性感染患者身上提取的血清是病毒的来源，将其以10-1、10-3和10-7的稀释度接种到三只黑猩猩身上。所有三只黑猩猩都患上了急性B型肝炎，血清中肝酶的峰值相对较高（高峰）。通过酶促扩增从黑猩猩血清中回收的病毒DNA的完整核苷酸序列与人血清中的序列相同。通过比较该株（HT）与32个已发表的HBV基因组的序列，确定了在其他HBV分离株中很少或从未发现的核苷酸和预测氨基酸的变化。十三个这样的核苷酸被发现内thecis-acting调节元件，其中6个内的增强子II-核心启动子区域。在开放阅读框中发现了24个罕见或独特的氨基酸变化，其中15个发生在跨越X基因3′端的区域，通过前核心/核心基因，到聚合酶基因的5′端。因此，涉及暴发性肝炎的HBV前核心终止突变体是高度传染性的，在黑猩猩中诱导重度肝炎，并且与报道的HBV分离株具有显著的遗传变异。
Hepatitis B virus (HBV) with an in-frame stop codon within the pre-core region of the virus genome caused fulminant hepatitis in two individuals. Serum from a chronically infected patient who was the source of the virus was inoculated into three chimpanzees at dilutions of 10-1, 10-3, and 10-7. All three chimpanzees developed acute hepatitis B with relatively high peak values of liver enzymes in their serum. The complete nucleotide sequence of virus DNA recovered from the chimpanzee serum by enzymatic amplification was identical with that from the human serum. By comparing the sequence of this strain (HT) with that of 32 published HBV genomes, changes in nucleotides and predicted amino acids that were rarely or never found in other HBV isolates were identified. Thirteen such nucleotides were found within thecis-acting regulatory elements, of which 6 were within the enhancer II-core promoter region. Twenty-four rare or unique changes in amino acids were found in open reading frames, of which 15 occurred in the region that spanned the 3′ half of the X gene, through the pre-core/core gene, to the 5′ end of the polymerase gene. Thus, an HBV pre-core stop mutant implicated in fulminant hepatitis is highly infectious, induces severe hepatitis in chimpanzees, and possesses significant genetic variation from reported HBV isolates.