Résumé
An important aspect of the infection by the human immunodeficiency virus (HIV-1) type 1 is its clinical latency, suggesting that the virus itself or the provirus may remain latent for extended periods of time after primary infection. Certain heterologous viral proteins or chemical and physical agents are able to reactivate latent virus. Since a common denominator shared by these agents is the ability to cause stress response in cells, we have examined the effects of oxidative stress mediated by hydrogen peroxide (H202) on HIV-1 latently infected promonocytic cell line termed U1. After exposure to H202 in concentrations ranging from 0.1 to 2 mM, the viability of the U1 cells decreased during 24 h before recovery. At 24 h post stress, the U1 cells began to express virus as assessed by elevated reverse transcriptase activities in culture supernatants. Immunofluorescence carried out on stressed U1 cells using anti-HIV-1 polyclonal antibodies showed that H202 leads to HIV-1 gene expression activation, but not to a release of viral particles from damaged cells. Additionally, using a HeLa cell line containing integrated the bacterial chloramphenicol acetyl transferase (CAT) gene under the control of the HIV-1 long terminal repeat (LTR), we have shown that oxidative stress mediated by H202 allows transactivation of the viral LTR revealed by intracellular CAT activity. A stimulation factor of around 4 of CAT activity can be reached when these cells are treated with 0.5 mM H202. A lower stimulation factor of CAT activity can be obtained when oxidative stress is mediated by stimulated phagocytes. During inflammatory reactions, blood cells containing latent virus can be exposed to activated oxygen species released by stimulated leukocytes and such a stress could convert a latent into a productive infection, leading to the development of the acquired immune deficiency syndrome.