6th International AIDS Conference


San Francisco, California, USA — June 20-23, 1990

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Tissue-specific activation of the HIV-1 long terminal repeat (LTR) by morphine in transgenic mice.

Int Conf AIDS 1990 Jun 20-23; 6:340 (abstract no. 1105)
Prakash O, Mukherjee PK, Wang TY, Mondal D, Coleman R; Laboratory of Molecular Oncology, Alton Ochsner Medical Foundation, New Orleans, Louisiana, USA

OBJECTIVE: To determine the cofactors in the in vivo induction of HIV expression.

METHODS: We have generated 4 strains of transgenic mice from founder animals carrying the HIV-1 LTR fused to the bacterial chloramphenicol acetyl transferase (CAT) reporter gene. CAT activities (percent conversion of 14C-chloramphenicol into the acetylated forms) in the various tissues of morphine-treated and -untreated animals were compared.

RESULTS: The mice in strains 1 and 2 show undetectable levels of CAT expression in the organs, whereas mice in strains 3 and 4 show highest levels (3-6% conversion per 100 ug protein/16 hours) in the thymus, spleen and spinal cord. Lower levels (less than 0.5% conversion) were detectable in the other organs. However, when the mice in all the 4 strains were injected intraperitoneally with a single daily dose of morphine sulphate (200 mg/kg body weight) for 4 days, substantial CAT gene expression (2-7% conversion in strains 1 and 2; 30-60% conversion in strains 3 and 4) was observed in brain, spinal cord and eyes of the morphine-treated animals. The morphine-induced CAT expression in the brain was limited to only hypothalamus and mid-brain. A lower response was observed when lower doses of morphine were used.

CONCLUSION: Our studies suggest that morphine and perhaps other opiates might directly alter susceptibility of an individual to HIV infection and development of AIDS-related symptoms. Studies are now underway to understand the in vivo activation of the HIV-1 LTR by morphine.

Keywords: AEGIS, HIV Long Terminal Repeat, Mice, Transgenic, Morphine, Gene Expression Regulation, Viral, Genes, Reporter, HIV, Acquired Immunodeficiency Syndrome, Narcotics, Gene Expression, Gene Expression Regulation, Mice, Animal, Cats, genetics, ICA6KWDaegis,hivlongterminalrepeat,mice,transgenic,morphine,geneexpressionregulation,viral,genes,reporter,hiv,acquiredimmunodeficiencysyndrome,narcotics,geneexpression,geneexpressionregulation,mice,animal,cats,genetics,ica6

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Copyright © 1990 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.