Sensitization of the HIV-1-LTR upon long term low dose oxidative stress.
Human lymphoid cell lines were transfected with HIV-1-LTR-CAT DNA and permanently transformed cell lines were obtained. These transformed cell lines were treated with 0.01 mM H2O2 for 25 days and the chloramphenicol acetyltransferase (CAT) activities of these cell lines were measured. The CAT activities of transformed cell lines were latent in normal culture conditions, but were activated by retreatment with 0.2 mM H2O2 for 1 h. On treatment with 0.05 mM H2O2 for 1 h, the CAT activity of these cell lines maintained in normal conditions remained latent, whereas cell lines pretreated with 0.01 mM H2O2 for 25 days were greatly activated by this treatment. Here, the HIV-1 promoter seemed latent in normal culture conditions, but it could be activated by a comparatively low concentration (0.05 mM) of H2O2 after treatment with a dilute H2O2 (0.01 mM) for about 1 month. Many patients infected with human immunodeficiency virus 1 (HIV-1) show a long latent period before development of AIDS. During this latent period, their infected cells may be subjected to oxidative stress due to metabolism and physical movement. The present results indicate that oxidative stress may cause activation of the HIV-1 promoter in patients with latent HIV-1.
Kurata
S i
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Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo 113, Japan.
D001483:Base Sequence; D001665:Binding Sites; D002461:Cell Line, Transformed; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016322:HIV Enhancer; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D014162:Transfection
D004279:DNA, Viral; D016328:NF-kappa B; D006861:Hydrogen Peroxide; D015500:Chloramphenicol O-Acetyltransferase