Human immunodeficiency virus long terminal repeat responds to transformation by the mutant T24 H-ras1 oncogene and it contains multiple AP-1 binding TPA-inducible consensus sequence elements.
We have employed a short term transfection assay to examine the response of HIV-1 LTR to transformation by the human normal and mutant T24 H-ras1 genes. The plasmid pBC12HIVCAT which carries the HIV-1 LTR sequences linked to the reporter gene chloramphenicol acetyl transferase (CAT) was transfected into rat 208F fibroblasts and their derivatives RFHO6N1-1 and RFHO6T1-1 transfectants. RFHO6N1-1 and RFHO6T1-1 express an exogenous human normal or mutant T24 H-ras1 gene respectively. Expression of the mutant T24 but not the normal H-ras1 gene resulted in increased levels of HIV-1 LTR driven CAT activity. We have noted four motifs in the HIV-1 LTR region which resemble TPA-inducible and AP-1 binding consensus sequences. Since H-ras1 fos and jun/AP-1 respond to TPA and T24 H-ras1 is known to induce both fos and jun/AP-1 nuclear transcriptional factors, it is possible that the latter genes play a role in HIV-1 transcription. Moreover, H-ras1 oncogene activation may play an important role in HIV gene expression and in the activation of latent HIV.
Spandidos
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DA
Beatson Institute for Cancer Research, Glasgow, Scotland, U.K.
Yiagnisis
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Pintzas
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D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics*; D011905:Genes, ras; D006678:HIV / Q000235:genetics*; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology; D014162:Transfection
D004279:DNA, Viral; D014157:Transcription Factors; D013755:Tetradecanoylphorbol Acetate