NATURALLY-OCCURRING MISSENSE MUTATION IN THE POLYMERASE GENE TERMINATING HEPATITIS-B VIRUS-REPLICATION
NATURALLY-OCCURRING MISSENSE MUTATION IN THE POLYMERASE GENE TERMINATING HEPATITIS-B VIRUS-REPLICATION
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DOI：
10.1128/jvi.65.4.1836-1842.1991
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发表时间：
1991-04-01
影响因子：
5.4
通讯作者：
WANDS, JR
中科院分区：
文献类型：
--
作者：
BLUM, HE;GALUN, E;WANDS, JR
从人肝组织中克隆了B型肝炎病毒（HBV）全基因组。 所有病毒基因中的许多突变将这种HBV DNA定义为突变体，与所有已知的HBV DNA序列不同。 该突变体的功能分析证明了阻断病毒DNA合成的缺陷。 该缺陷的遗传基础被鉴定为病毒聚合酶基因5'区域中的单个错义突变，导致不能将前基因组RNA包装到核心颗粒中。 复制缺陷可以被全长野生型聚合酶基因构建体反式互补，但不能被全长突变体或3 '截短的野生型聚合酶基因构建体反式互补。 我们的研究结果表明，在病毒的生命周期中的5'聚合酶基因区域的关键作用，并建议在该区域引入错义突变可以是一种策略，以终止病毒在体内复制。
A hepatitis B virus (HBV) genome was cloned from human liver. Numerous mutations in all viral genes define this HBV DNA as a mutant, divergent from all known HBV DNA sequences. Functional analyses of this mutant demonstrated a defect blocking viral DNA synthesis. The genetic basis of this defect was identified as a single missense mutation in the 5' region of the viral polymerase gene, resulting in the inability to package pregenomic RNA into core particles. The replication defect could be trans-complemented by a full-length wild-type, but not by a full-length mutant or 3'-truncated wild-type, polymerase gene construct. Our findings indicate a critical role of the 5' polymerase gene region in the life cycle of the virus and suggest that introducing missense mutations in this region can be a strategy to terminate viral replication in vivo.