Triggering of apoptosis is not sufficient to induce human immunodeficiency virus gene expression.
We examined whether there is any causative link between apoptosis and HIV gene expression elicited in response to ultraviolet light (UV) and ionizing radiation (IR). We found that both UV and IR activate HIV gene expression in human T lymphoblastoid 1G5 (HIVluc) cells, but with different kinetics and magnitudes. Treatment with either type of radiation resulted in increased apoptosis, which correlated closely with HIV gene expression. The involvement of caspases in the IR response was demonstrated by using zVAD-FMK and zDEVD-FMK caspase inhibitors; both apoptosis and HIV gene expression were inhibited to similar extent. Surprisingly, treatment of 1G5 cells with FAS antibody triggered apoptosis but did not increase HIV gene expression. A correlation between increased apoptosis and gene expression was also demonstrated in human carcinoma HIVcat/A549 cells with UV whereas IR triggered apoptosis but did not activate HIV gene expression. Most significantly, UV activation of HIV gene expression, and NF-kappa-B and p38 MAP kinase, both important for efficient HIV gene expression, were not affected by treatment with the zVAD-FMK and zDEVD-FMK inhibitors. Treatment of HIVcat/A549 cells with staurosporine or scrape-loading of cells with cytochrome c resulted in apoptosis but no increase in HIV gene expression. Altogether, a direct correlation exists between apoptosis and HIV gene expression in T-cells in response to both UV and IR but this is not the case in carcinoma cells. Triggering of apoptosis per se in either cell type does not necessarily result in increased HIV gene expression. Most importantly, the apoptotic and HIV gene expression responses elicited by UV are different to some extent and can be separated.
Oakley
Jacqueline D
JD
Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.
Taher
Mohiuddin M
MM
Hershey
Chad M
CM
Aggarwal
Puneet C
PC
Estwani
Isam B
IB
Valerie
Kristoffer
K
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006678:HIV / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007259:Infrared Rays; D019169:Jurkat Cells; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D011839:Radiation, Ionizing; D013997:Time Factors; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D016328:NF-kappa B; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D006861:Hydrogen Peroxide; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases