Activation of the HIV type 1 long terminal repeat and viral replication by dimethylsulfoxide and related solvents.
The HIV-1 long terminal repeat (LTR) introduced into the macrophage cell line THP-1 and the T lymphocyte cell line Jurkat in association with the luciferase reporter gene is activated by the polar, aprotic solvents dimethylsulfoxide (DMSO), dimethylacetamide (DMAC), and dimethylformamide (DMF). These solvents also greatly potentiated the activation of the LTR in THP-1 cells by phorbol myristate acetate (PMA), tumor necrosis factor alpha (TNF-alpha), H202, and a Staphylococcus epidermidis product. Lipopolysaccharide (LPS) and lipoteichoic acid (LTA) at 1 microg/ml had no effect on the LTR in THP-1 cells unless the solvents were added. The aprotic solvents also greatly potentiated the activation of the LTR in Jurkat cells by PMA, TNF-alpha, and H202, whereas LPS, LTA, or the S. epidermidis product had no effect in the presence or absence of the solvents. DMSO, DMAC, and DMF also increased the production of intact virions by latently HIV-1-infected ACH-2, J1.1, U1, and OM10.1 cells under some experimental conditions. The use of the polar aprotic solvents DMSO, DMAC, and DMF, by amplification, may allow the better detection of a weak activator of the LTR and facilitate studies of the mechanism of activation.
Klebanoff
S J
SJ
Department of Medicine, University of Washington, Seattle 98195-7185, USA.
Mehlin
C
C
Headley
C M
CM
D000081:Acetamides / Q000494:pharmacology; D003451:Cryoprotective Agents / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004126:Dimethylformamide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D016325:HIV Long Terminal Repeat / Q000187:drug effects* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019169:Jurkat Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D012997:Solvents / Q000494:pharmacology*; D013682:Teichoic Acids / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D000081:Acetamides; D003451:Cryoprotective Agents; D008070:Lipopolysaccharides; D012997:Solvents; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid; D004126:Dimethylformamide; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide