Suppressive effect of liposomes containing DNA coding for diphtheria toxin A-chain on cells transformed with bovine leukemia virus.
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.
Kakidani
H
H
Biotechnology Research Laboratory, TOSOH Corporation, Kanagawa, Japan.
Watarai
S
S
Onuma
M
M
Tomochika
K
K
Yasuda
T
T
D000818:Animals; D002459:Cell Fusion / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004269:DNA, Bacterial / Q000494:pharmacology*; D004167:Diphtheria Toxin / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D004337:Drug Carriers; D015967:Gene Expression Regulation, Viral; D001909:Leukemia Virus, Bovine / Q000187:drug effects*; D008081:Liposomes / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012756:Sheep; D014162:Transfection / Q000187:drug effects
D004269:DNA, Bacterial; D004167:Diphtheria Toxin; D004337:Drug Carriers; D008081:Liposomes