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转基因小鼠中的乙肝病毒产生

HBV production in transgenic mice.

作者信息

Yamamura K, Araki K, Hino O, Tomita N, Miyazaki J, Matsubara K

机构信息

Institute for Medical Genetics, Kumamoto University Medical School, Japan.

出版信息

Gastroenterol Jpn. 1990 Sep;25 Suppl 2:49-52. doi: 10.1007/BF02779928.

DOI:10.1007/BF02779928
PMID:2227265
Abstract

We produced transgenic mice by microinjecting a partially duplicated copies of hepatitis B virus (HBV) gene into fertilized eggs of C57BL/6 mice. One mouse was a high producer of HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the serum. All offspring carrying HBV DNA were positive for both antigens in the serum. The HBV DNA was expressed in liver- and kidney-specific manner. The normal process of HBV replication, including the packaging of the pregenome 3.5-kb RNA into a nucleocapsid, the reverse-transcription of the complete minus strand DNA, and the release of Dane particles into the serum before the completion of synthesis of plus strand, occurred in the liver of these transgenic mice. These results suggest that the species specificity of HBV infection is not due to the inability to replicate in nonnatural host but to the lack of receptors or factors needed for virus adsorption and internalization. The founder mouse is now 19 months of age but shows no clinical or pathological change, suggesting that HBV itself is not cytopathic.

摘要

我们通过将部分重复的乙型肝炎病毒(HBV)基因显微注射到C57BL/6小鼠的受精卵中,培育出了转基因小鼠。有一只小鼠血清中的HBV表面抗原(HBsAg)和HBV e抗原(HBeAg)产量很高。所有携带HBV DNA的后代血清中的这两种抗原均呈阳性。HBV DNA以肝脏和肾脏特异性的方式表达。这些转基因小鼠的肝脏中发生了HBV复制的正常过程,包括将前基因组3.5 kb RNA包装进核衣壳、完整负链DNA的逆转录以及在正链合成完成之前将 Dane 颗粒释放到血清中。这些结果表明,HBV感染的物种特异性并非由于无法在非天然宿主中复制,而是由于缺乏病毒吸附和内化所需的受体或因子。这只奠基小鼠现在19个月大,但未出现临床或病理变化,表明HBV本身没有细胞病变作用。

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Production and effect of infectious Dane particles in transgenic mice.传染性 Dane 颗粒在转基因小鼠中的产生及作用
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引用本文的文献

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Hepatocellular carcinoma mouse models: Hepatitis B virus-associated hepatocarcinogenesis and haploinsufficient tumor suppressor genes.肝细胞癌小鼠模型:乙型肝炎病毒相关的肝癌发生及单倍体不足的肿瘤抑制基因
World J Gastroenterol. 2016 Jan 7;22(1):300-25. doi: 10.3748/wjg.v22.i1.300.
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A short N-proximal region in the large envelope protein harbors a determinant that contributes to the species specificity of human hepatitis B virus.大包膜蛋白中的一个短的N近端区域含有一个决定因素,该因素有助于人类乙型肝炎病毒的种属特异性。
J Virol. 2001 Dec;75(23):11565-72. doi: 10.1128/JVI.75.23.11565-11572.2001.

本文引用的文献

1
Introduction of human gamma 1 immunoglobulin genes into fertilized mouse eggs.将人类γ1免疫球蛋白基因导入受精的小鼠卵中。
J Biochem. 1984 Aug;96(2):357-63. doi: 10.1093/oxfordjournals.jbchem.a134845.
2
A human hepatitis B viral enhancer element.一种人类乙型肝炎病毒增强子元件。
EMBO J. 1985 Feb;4(2):427-30. doi: 10.1002/j.1460-2075.1985.tb03646.x.
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Specific expression of hepatitis B surface antigen (HBsAg) in transgenic mice.乙型肝炎表面抗原(HBsAg)在转基因小鼠中的特异性表达。
Science. 1985 Dec 6;230(4730):1160-3. doi: 10.1126/science.3865370.
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A transgenic mouse model of the chronic hepatitis B surface antigen carrier state.
Science. 1985 Dec 6;230(4730):1157-60. doi: 10.1126/science.3865369.
5
Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice.转基因小鼠中乙型肝炎病毒大包膜多肽合成的结构和病理效应
Proc Natl Acad Sci U S A. 1987 Oct;84(19):6909-13. doi: 10.1073/pnas.84.19.6909.
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The hepatitis B virus.乙型肝炎病毒
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Expression and replication of hepatitis B virus genome in transgenic mice.乙型肝炎病毒基因组在转基因小鼠中的表达与复制。
Proc Natl Acad Sci U S A. 1989 Jan;86(1):207-11. doi: 10.1073/pnas.86.1.207.
8
Replication and gene expression of hepatitis B virus in a transgenic mouse that contains the complete viral genome.乙型肝炎病毒在含有完整病毒基因组的转基因小鼠中的复制及基因表达。
J Virol. 1988 Nov;62(11):4144-52. doi: 10.1128/JVI.62.11.4144-4152.1988.
9
Tissue preferential expression of the hepatitis B virus (HBV) surface antigen gene in two lines of HBV transgenic mice.乙肝病毒(HBV)表面抗原基因在两系HBV转基因小鼠中的组织优先表达
J Virol. 1988 Feb;62(2):649-54. doi: 10.1128/JVI.62.2.649-654.1988.
10
Demethylation by 5-azacytidine results in the expression of hepatitis B virus surface antigen in transgenic mice.5-氮杂胞苷引起的去甲基化作用导致转基因小鼠中乙型肝炎病毒表面抗原的表达。
Jpn J Cancer Res. 1989 Apr;80(4):295-8. doi: 10.1111/j.1349-7006.1989.tb02308.x.