REPLICATING AND VIRION SECRETING HEPATITIS-B MUTANT VIRUS UNABLE TO PRODUCE PRES2 PROTEIN

REPLICATING AND VIRION SECRETING HEPATITIS-B MUTANT VIRUS UNABLE TO PRODUCE PRES2 PROTEIN
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DOI:
10.1016/0168-8278(91)90036-b
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发表时间:
1991-01-01
影响因子:
25.7
通讯作者:
WILL, H
WILL, H
中科院分区:
医学1区
文献类型:
--
作者:
FERNHOLZ, D;STEMLER, M;WILL, H

文献摘要

被引文献

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在高度病毒血症慢性携带者的血清中发现了无法产生前S2蛋白的突变型HBV基因组。通过对扩增的preS区域进行直接测序以及通过对50个克隆的扩增的preS DNA片段进行测序,发现所有分子都删除了preS2翻译起始密码子及其下游的3个氨基酸54个核苷酸。此外,还发现了许多氨基酸变化,主要位于两个缺失之间。含有突变的 preS 序列的 HBV-DNA 基因组被证明具有复制能力,并能有效分泌病毒粒子,这些病毒粒子在形态上和衣壳 DNA 类型上与野生型病毒没有区别。这些数据表明,具有突变的 preS 序列且无法表达 preS2 蛋白的 HBV 可以在高度病毒血症的慢性携带者中作为显性或排他性病毒群体出现。数据还表明,preS2 蛋白的表达对于 HBV 复制、病毒粒子形态发生和分泌并不是必需的。
Mutant HBV genomes unable to produce preS2 protein were identified in the serum of a highly viremic chronic carrier. By direct sequencing of the amplified preS region and by sequencing of 50 cloned amplified preS DNA fragments all molecules were found to have deleted the preS2 translation initiation codon and three amino acids 54 nucleotides downstream thereof. In addition, numerous amino acid changes, predominantly located between both deletions, were revealed. HBV-DNA genomes containing the mutated preS sequences were shown to be replication competent and to secrete efficiently virions that were morphologically and by the type of DNA encapsidated not distinguishable from wild-type virus. These data demonstrate that HBV with mutated preS sequences and unable to express preS2 protein can occur as a dominant or exclusive virus population in a highly viremic chronic carrier. The data also show that expression of the preS2 protein is not essential for HBV replication, virion morphogenesis and secretion.