TRANSFORMATION TO CONTINUOUS GROWTH OF PRIMARY HUMAN LYMPHOCYTES-T BY HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I X-REGION GENES TRANSDUCED BY A HERPESVIRUS-SAIMIRI VECTOR
TRANSFORMATION TO CONTINUOUS GROWTH OF PRIMARY HUMAN LYMPHOCYTES-T BY HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I X-REGION GENES TRANSDUCED BY A HERPESVIRUS-SAIMIRI VECTOR
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DOI：
10.1073/pnas.86.9.3351
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发表时间：
1989-05-01
影响因子：
11.1
通讯作者：
HASELTINE, WA
中科院分区：
文献类型：
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作者：
GRASSMANN, R;DENGLER, C;HASELTINE, WA
人T细胞白血病病毒I型（HTLV-1）基因组的X区在淋巴细胞永生化中的作用与其在病毒复制中的作用难以区分，因为该区域编码病毒蛋白复制和表达所需的至少两个基因tax和雷克斯。为了确定X区是否编码永生化功能，将能够表达已知X区蛋白的HTLV-1前病毒片段插入到转化缺陷型、复制能力型松鼠猴疱疹病毒的基因组中。感染新鲜的丝裂原活化的人脐带血和胸腺细胞产生具有相同表型（CD 4+、CD 5+、HLA II类+、白细胞介素2受体α-链+）作为通过与HTLV-1共培养转化的淋巴细胞。这些实验表明，X区域编码HTLV-I的功能，其使人T细胞的不同亚群永生化。实验也证明了H. saimiri载体用于将异源基因转导到人T细胞中。
The role of the X region of the genome of the human T-cell leukemia virus type I (HTLV-I) in the immortalization of lymphocytes has been been difficult to distinguish from its role in viral replication as this region encodes at least two genes, tax and rex, required for replication and the expression of viral proteins. To determine whether the X region does encode immortalizing functions, a fragment of the HTLV-1 provirus capable of expressing known X-region proteins was inserted into the genome of a transformation-defective, replication-competent Herpesvirus saimiri. Infection of fresh mitogen-activated human cord blood and thymocytes yielded immortal T-cell lines that had the same phenotype (CD4+, CD5+, HLA class II+, interleukin 2 receptor .alpha.-chain +) as lymphocytes transformed by cocultivation with HTLV-1. These experiments demonstrate that the X region encodes the functions of HTLV-I that immortalize a distinct subpopulation of human T cells. The experiments also demonstrate the utility of the H. saimiri vector for the transduction of heterologous genes into human T cells.