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A型内源性逆转录病毒的分子生物学

Molecular biology of type A endogenous retrovirus.

作者信息

Ono M

机构信息

Department of Molecular Biology, School of Medicine, Kitasato University, Kanagawa, Japan.

出版信息

Kitasato Arch Exp Med. 1990 Sep;63(2-3):77-90.

PMID:1710682
Abstract

Intracisternal A particles (IAPs) are retrovirus-like structures consistently observable in a variety of mouse tumor cells such as myeloma and hybridoma and in early embryonic cells derived from rodents but nothing is known of their infectivity. Mouse IAPs contain a gag-like protein, a reverse transcriptase and a polyadenylated RNA molecule (IAP RNA). DNA sequences complementary to IAP RNA (IAP genome) are interspersedly present in rodent such as mice, rats, Chinese hamsters and Syrian hamsters at several hundred to a thousand copies per haploid genome. Molecularly cloned IAP genomes from two species Mus and Syrian hamster were 6 to 8 kb in length with LTRs of about 0.4 kb long. The nucleotide sequence of the Syrian hamster IAP genome, H18, predicted a typical LTR-gag-prt-pol-env-LTR structure, although many stop codons were present in the region corresponding to env. The comparison of the deduced amino acid sequences of the pol region showed IAP (type A), mouse mammary tumor virus (MMTV) (type B), and squirrel monkey retrovirus (SMRV) (type D) genomes to be closely related. By using a DNA fragment encoding the pol region of the Syrian hamster IAP genome, human endogenous retroviruses termed HERV-K, were cloned from a fetal human liver gene library. Typical HERV-K genome was 9.5 kb in length having LTRs of about 1.0 kb. The HERV-K provirus could encode gag (666 codons), prt (334 codons), pol (937 codons), and env (618 codons) genes. HERV-K was shown to be closely related to types A, B and D retroviruses. The HERV-K genomes are present at about 50 copies per haploid human genome. In several human tumor cell lines, the HERV-K genome was expressed as 8.8 kb poly(A)+ RNA which appeared to be a full-size transcript of this genome. In the human breast cancer cell line T47D, stimulation of HERV-K genome expression was observed following female steroids treatment. In a detailed investigation on the organization of HERV-K proviruses in human genome, we found repetitive sequences homologous to the LTR region of the HERV-K genome. They were about 630 bp in length with an A rich tail at 3' end and found to be a SINE type nonviral retroposon. These elements were present at 4,000 to 5,000 copies per haploid human genome.

摘要

脑池内A颗粒(IAPs)是类似逆转录病毒的结构,在多种小鼠肿瘤细胞如骨髓瘤和杂交瘤以及源自啮齿动物的早期胚胎细胞中一直可以观察到,但对其感染性却一无所知。小鼠IAPs含有一种类gag蛋白、一种逆转录酶和一个多聚腺苷酸化的RNA分子(IAP RNA)。与IAP RNA互补的DNA序列(IAP基因组)以数百至每单倍体基因组一千个拷贝的形式散布在小鼠、大鼠、中国仓鼠和叙利亚仓鼠等啮齿动物中。从两个物种小家鼠和叙利亚仓鼠分子克隆的IAP基因组长度为6至8 kb,其长末端重复序列(LTRs)约0.4 kb长。叙利亚仓鼠IAP基因组H18的核苷酸序列预测为典型的LTR - gag - prt - pol - env - LTR结构,尽管在对应于env的区域存在许多终止密码子。pol区域推导的氨基酸序列比较表明,IAP(A型)、小鼠乳腺肿瘤病毒(MMTV)(B型)和松鼠猴逆转录病毒(SMRV)(D型)基因组密切相关。通过使用编码叙利亚仓鼠IAP基因组pol区域的DNA片段,从人胎儿肝脏基因文库中克隆出了称为HERV - K的人内源性逆转录病毒。典型的HERV - K基因组长度为9.5 kb,其LTRs约1.0 kb。HERV - K前病毒可编码gag(666个密码子)、prt(334个密码子)、pol(937个密码子)和env(618个密码子)基因。已表明HERV - K与A、B和D型逆转录病毒密切相关。HERV - K基因组以每单倍体人类基因组约50个拷贝的形式存在。在几种人类肿瘤细胞系中,HERV - K基因组表达为8.8 kb的多聚腺苷酸化RNA,这似乎是该基因组的全长转录本。在人乳腺癌细胞系T47D中,在雌性类固醇处理后观察到HERV - K基因组表达的刺激。在对HERV - K前病毒在人类基因组中的组织进行的详细研究中,我们发现了与HERV - K基因组LTR区域同源的重复序列。它们长度约为630 bp,3'端有一个富含A的尾巴,并且被发现是一种SINE型非病毒逆转座子。这些元件以每单倍体人类基因组4000至5000个拷贝的形式存在。

相似文献

1
Molecular biology of type A endogenous retrovirus.A型内源性逆转录病毒的分子生物学
Kitasato Arch Exp Med. 1990 Sep;63(2-3):77-90.
2
Defective endogenous retrovirus-like sequences and particles of Chinese hamster ovary cells.中国仓鼠卵巢细胞中缺陷性内源性逆转录病毒样序列和颗粒
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Genomic distribution and transcription of solitary HERV-K LTRs.孤立的人内源性逆转录病毒K长末端重复序列的基因组分布与转录
Genomics. 1993 Nov;18(2):261-9. doi: 10.1006/geno.1993.1464.
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Characterization of human endogenous retrovirus type K virus-like particles generated from recombinant baculoviruses.源自重组杆状病毒的人内源性K型逆转录病毒样颗粒的特性分析
Virology. 1997 Jul 7;233(2):280-91. doi: 10.1006/viro.1997.8614.
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Expression of human endogenous retrovirus k envelope transcripts in human breast cancer.人类内源性逆转录病毒K包膜转录本在人乳腺癌中的表达
Clin Cancer Res. 2001 Jun;7(6):1553-60.
6
A general method for the identification of transcribed retrovirus sequences (R-U5 PCR) reveals the expression of the human endogenous retrovirus loci HERV-H and HERV-K in teratocarcinoma cells.一种用于鉴定转录逆转录病毒序列的通用方法(R-U5 PCR)揭示了人内源性逆转录病毒基因座HERV-H和HERV-K在畸胎瘤细胞中的表达。
Virology. 1993 Feb;192(2):501-11. doi: 10.1006/viro.1993.1066.
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Structure and genomic organization of a novel human endogenous retrovirus family: HERV-K (HML-6).一种新型人类内源性逆转录病毒家族:HERV-K(HML-6)的结构与基因组组织
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HERV-H endogenous retroviruses: presence in the New World branch but amplification in the Old World primate lineage.HERV-H内源性逆转录病毒:存在于新大陆分支中,但在旧大陆灵长类谱系中扩增。
Virology. 1995 Nov 10;213(2):395-404. doi: 10.1006/viro.1995.0012.
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Molecular cloning and long terminal repeat sequences of human endogenous retrovirus genes related to types A and B retrovirus genes.与A、B型逆转录病毒基因相关的人类内源性逆转录病毒基因的分子克隆及长末端重复序列
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HERV-K-T47D-Related long terminal repeats mediate polyadenylation of cellular transcripts.与HERV-K-T47D相关的长末端重复序列介导细胞转录本的聚腺苷酸化。
Genomics. 2000 May 15;66(1):98-103. doi: 10.1006/geno.2000.6175.

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