Naturally occurring woodchuck hepatitis virus (WHV) deletion mutants in chronically WHV-infected woodchucks.
Naturally occurring woodchuck hepatitis virus (WHV) deletion mutants in chronically WHV-infected woodchucks.
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长期感染土拨鼠肝炎病毒 (WHV) 的土拨鼠中自然存在 WHV 缺失突变体。
作者：
A. Botta;M. Lu;X. Zhen;T. Kemper;M. Roggendorf
B型肝炎病毒（HBV）的缺失突变体常在慢性HBV感染患者中发现。目前还不可能在合适的动物模型中研究这种缺失突变体对肝脏疾病的意义。在这项研究中，我们的特点是自然发生的土拨鼠肝炎病毒（WHV）在11慢性WHV感染的土拨鼠缺失突变体。WHV preS区域（nt 2992-338）内的缺失长度为72或84 bp，位于preS 1的氨基末端部分。核心基因（CID）内的内部缺失具有可变长度（103至312 bp），并在该基因的中心（nt 2021-2587）内鉴定。7个CID中有4个是框内缺失，而其余3个CID是框外缺失，导致阅读框中断。克隆的CIDs PCR产物的序列分析表明，异质性WHV缺失突变体共存于单个土拨鼠。此外，在WHV基因组中还发现了前S1和核心区双缺失的基因组，转染实验中未检测到截短核心蛋白的表达。CID突变导致与WHV聚合酶起始密码子融合的荧光素酶基因的表达显著增加，这可能是由于非翻译区的缩短或聚合酶起始密码子之前的AUG的去除。自然发生的WHV缺失突变体的特性将使我们能够在未来的土拨鼠模型中研究其生物学和致病特性。
Deletion mutants of hepatitis B virus (HBV) are often found in chronically HBV-infected patients. It has not been possible to study the significance of such deletion mutants on liver diseases in a suitable animal model. In this study, we characterized naturally occurring deletion mutants of woodchuck hepatitis virus (WHV) in 11 chronically WHV-infected woodchucks. Deletions within the WHV preS region (nt 2992-338) had a length of 72 or 84 bp and were located in the amino terminal part of preS1. Internal deletions within the core gene (CID) had variable lengths (103 to 312 bp) and were identified within the center of this gene (nt 2021-2587). Four of seven CIDs were in-frame deletions, whereas the remaining three CIDs were out-of-frame deletions and led to the interruption of the reading frame. Sequence analysis of cloned PCR products of CIDs showed that heterogeneous WHV deletion mutants coexisted in single woodchucks. In addition, WHV genomes with double deletions in the preS1 and the core region could be found. We were unable to detect the expression of truncated core proteins in transfection experiments. The CID mutations led to a marked increase of the expression of the luciferase gene which was fused to the start codon of WHV polymerase, probably due to the shortening of the untranslated region or the removal of AUGs preceding the polymerase start codon. The characterization of naturally occurring WHV deletion mutants will allow us to study their biological and pathogenic properties in the woodchuck model in the future.
乙型肝炎病毒前 S1 缺失突变体的特性。
影响因子：
3.7
作者：
Melegari,M;Bruno,S;Wands,JR
通讯作者：
Wands,JR
土拨鼠的实验性 WHV 感染：嗜肝DNA病毒诱发肝癌的动物模型。
DOI：
10.1007/bf02779926
发表时间：
1990
期刊：
Gastroenterologia Japonica
影响因子：
--
作者：
Gerin,JL
通讯作者：
Gerin,JL