HIV-1 promoter activation following an oxidative stress mediated by singlet oxygen.
Various biological processes, such as photosensitization or inflammatory reactions, can generate singlet oxygen (1O2) as one of the major oxidative species. Because this oxidant can be generated either extracellularly or intracellularly, it can cause severe damage to various biological macromolecules, even to those deeply embedded inside the cells such as DNA. Sublethal biological modifications induced by different DNA-damaging agents can promote various cellular responses initiated by the activation of various cellular genes and certain heterologous viruses. Since 1O2 fulfils essential prerequisites for a genotoxic substance, we have examined the effects of an oxidative stress, mediated by this species, on cells harbouring a heterologous promoter-leader sequence derived from the human immunodeficiency virus type 1 (HIV-1). Our results demonstrate that HIV-1 long terminal repeat (LTR), integrated into the cellular DNA of epithelial cells, can be transactivated following an oxidative stress mediated by 1O2. In addition, using HIV-1 latently infected promonocytes or lymphocytes, it can be shown that virus reactivation can be induced through a sublethal dose of 1O2 generated intracellularly. An extracellular generation of 1O2 can promote a substantial lethal effect without HIV-1 reactivation. These data may be relevant to the understanding of the events converting a latent infection into a productive one and to the appearance of the acquired immune deficiency syndrome.
Legrand-Poels
S
S
Laboratory of Virology, Institute of Pathology, University of Liège, Belgium.
Hoebeke
M
M
Vaira
D
D
Rentier
B
B
Piette
J
J
D002470:Cell Survival / Q000528:radiation effects; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008027:Light; D010100:Oxygen / Q000494:pharmacology*; D010777:Photochemistry; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000528:radiation effects; D026082:Singlet Oxygen; D015533:Transcriptional Activation; D014162:Transfection; D016662:Virus Integration
D026082:Singlet Oxygen; D015500:Chloramphenicol O-Acetyltransferase; D010100:Oxygen