HUMAN ADULT T-CELL LEUKEMIA-VIRUS - COMPLETE NUCLEOTIDE-SEQUENCE OF THE PROVIRUS GENOME INTEGRATED IN LEUKEMIA-CELL DNA

HUMAN ADULT T-CELL LEUKEMIA-VIRUS - COMPLETE NUCLEOTIDE-SEQUENCE OF THE PROVIRUS GENOME INTEGRATED IN LEUKEMIA-CELL DNA
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DOI:
10.1073/pnas.80.12.3618
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发表时间:
1983-01-01
期刊:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子:
--
通讯作者:
YOSHIDA, M
YOSHIDA, M
中科院分区:
其他
文献类型:
--
作者:
SEIKI, M;HATTORI, S;YOSHIDA, M

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人类逆转录病毒成人T细胞白血病病毒(ATLV)已被证明与人类成人T细胞白血病(ATL)密切相关。对整合在ATL患者白血病T细胞DNA中的ATLV前病毒进行了分子克隆,并测定了前病毒基因组9032个碱基的完整核苷酸序列。前病毒DNA含有2个长末端重复序列(LTR),由755个碱基组成,每端一个,其侧翼是细胞DNA序列的6个碱基的直接重复序列。LTR中的核苷酸可以排列成独特的二级结构,这可以解释3“LTR中而不是5”LTR中的转录终止。原病毒的核苷酸序列包含3个大的开放阅读框,其能够编码48,000、99,000和54,000道尔顿的蛋白质。这3个开放框是从病毒基因组的5“末端开始的顺序,并且预测的48,000-道尔顿多肽是gag蛋白的前体,因为它具有与人T细胞白血病病毒(HTLV)p24的NH 2末端相同的氨基酸序列。编码99,000-和54,000-道尔顿多肽的开放框架被认为分别是pol和env基因。在这3个开放框架的3“侧,ATLV序列在不同阶段具有4个较小的开放框架;这些框架可编码10,000-、11,000-、12,000-和27,000-道尔顿多肽。虽然这些开放框架中的一个或一些可能是该病毒的转化基因,但初步分析,该区域的DNA与正常人类基因组没有同源性。
Human retrovirus adult T-cell leukemia virus (ATLV) has been shown to be closely associated with human adult T-cell leukemia (ATL). The provirus of ATLV integrated in DNA of leukemia T cells from a patient with ATL was molecularly cloned and the complete nucleotide sequence of 9032 bases of the proviral genome was determined. The provirus DNA contains 2 long terminal repeats (LTR) consisting of 755 bases, one at each end, which are flanked by a 6-base direct repeat of the cellular DNA sequence. The nucleotides in the LTR could be arranged into a unique secondary structure, which could explain transcriptional termination within the 3'' LTR but not in the 5'' LTR. The nucleotide sequence of the provirus contains 3 large open reading frames, which are capable of coding for proteins of 48,000, 99,000 and 54,000 daltons. The 3 open frames are in this order from the 5'' end of the viral genome and the predicted 48,000-dalton polypeptide is a precursor of gag proteins, because it has an identical amino acid sequence to that of the NH2 terminus of human T-cell leukemia virus (HTLV) p24. The open frames coding for 99,000- and 54,000-dalton polypeptides are thought to be the pol and env genes, respectively. On the 3'' side of these 3 open frames, the ATLV sequence has 4 smaller open frames in various phases; these frames may code for 10,000-, 11,000-, 12,000- and 27,000-dalton polypeptides. Although one or some of these open frames could be the transforming gene of this virus, in preliminary analysis, DNA of this region has no homology with the normal human genome.