A human T lymphotropic virus type I (HTLV-I) long terminal repeat-directed antisense c-myc construct with an Epstein-Barr virus replicon vector inhibits cell growth in a HTLV-I-transformed human T cell line.
A panel of EB virus replicon-based vectors was constructed to examine the relative utility of four distinct eukaryotic promoters for high-level gene expression in a HTLV-I-transformed human T cell line, HUT102. We found that HTLV-I LTR, which is trans-activated by the viral tax protein, was most suited for EBV vector-based stable gene expression in it. We prepared a HTLV-I LTR-directed antisense c-myc construct with an EBV vector. This antisense plasmid suppressed c-myc expression and inhibited growth of HUT102 cells in vitro with unaltered expression of tax. Non-specific plasmid toxicity was excluded by showing that the antisense construct had little effect on growth and c-myc expression of HTLV-I-negative Jurkat T cells, in which the viral LTR is expected to be less active. Our results indicate that c-myc may play an important role in the deregulated growth of HTLV-I-transformed T cells.
Fujita
M
M
Department of Oncology, Nagasaki University School of Medicine, Japan.
Shiku
H
H
D000199:Actins / Q000235:genetics; D001769:Blood; D002455:Cell Division / Q000235:genetics; D002472:Cell Transformation, Viral; D005814:Genes, Viral; D016259:Genes, myc; D005822:Genetic Vectors; D004854:Herpesvirus 4, Human / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012093:Replicon; D013601:T-Lymphocytes / Q000166:cytology*; D014158:Transcription, Genetic; D014162:Transfection
D000199:Actins; D016372:RNA, Antisense