SUPPRESSIVE EFFECT OF LIPOSOMES CONTAINING DNA CODING FOR DIPHTHERIA TOXIN-A-CHAIN ON CELLS TRANSFORMED WITH BOVINE LEUKEMIA-VIRUS
SUPPRESSIVE EFFECT OF LIPOSOMES CONTAINING DNA CODING FOR DIPHTHERIA TOXIN-A-CHAIN ON CELLS TRANSFORMED WITH BOVINE LEUKEMIA-VIRUS
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DOI：
10.1111/j.1348-0421.1993.tb01696.x
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发表时间：
1993-01-01
影响因子：
2.6
通讯作者：
YASUDA, T
中科院分区：
文献类型：
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作者：
KAKIDANI, H;WATARAI, S;YASUDA, T
为探索脂质体作为抗病毒药物的新用途，构建了含牛白血病病毒（BLV）长末端重复序列（LTR）控制的白喉毒素A链（DT-A）基因的重组质粒（BLV-LTR）。BLV-LTR的启动子活性通过氯霉素乙酰转移酶（CAT）测定来估计，所述测定使用含有在BLV-LTR控制下的CAT的编码序列的质粒（pBLVCAT）。当用pBLVCAT转染BLV感染的细胞时，检测到CAT活性。BLV未感染的细胞系，然而，没有检测到CAT活性。将包埋在脂质体中的质粒DNA加入培养的BLV感染的细胞中。在BLV-LTR的控制下，含有DT-A基因的脂质体有效地抑制了BLV感染细胞诱导的合胞体形成。相反，含有DT-A基因而没有启动子的脂质体没有显示出这种效果。含BLV LTR的DT-A基因脂质体不影响牛免疫缺陷病毒诱导的合胞体形成。这些观察结果表明，BLV感染的细胞很容易在基因表达水平上被靶向。这种策略可以应用于治疗BLV诱导的牛B细胞增殖，并进一步应用于其他病毒/肿瘤疾病，其中发挥特定的基因表达。
A recombinant plasmid which contained a gene for diphtheria toxin A-chain (DT-A) under the control of the long terminal repeat (LTR) of bovine leukemia virus (BLV) (BLV-LTR) was constructed to test a novel application of liposomes as antiviral agents. The promoter activity of BLV-LTR was estimated by the chloramphenicol acetyltransferase (CAT) assay using a plasmid which contains the coding sequence of CAT under the control of BLV-LTR (pBLVCAT). When BLV-infected cells were transfected with pBLVCAT, CAT activity was detected. BLV-uninfected cell lines, however, showed no detectable CAT activity. The plasmid DNA entrapped in liposomes was added to BLV-infected cells in culture. Syncytium formation induced by BLV-infected cells was effectively suppressed by the liposomes containing the gene for DT-A under the control of BLV-LTR. Conversely, liposomes containing the gene for DT-A without a promoter showed no such effect. DT-A gene-containing liposomes with BLV-LTR did not affect formation of syncytium induced by bovine immunodeficiency virus. These observations indicate that BLV-infected cells were readily targeted on the level of gene expression. This strategy could be applied to the treatment of BLV-induced B-cell proliferation of cattle, and further to other viral/neoplastic diseases where specific gene expression is exerted.