Triggering of Apoptosis is not Sufficient to Induce Human Immunodeficiency Virus Gene Expression

Abstract

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‐ κB 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. IUBMB Life, 55: 415‐427, 2003

HIV gp120 Induces, NF-κB Dependent, HIV Replication that Requires Procaspase 8

“…Such data link apoptosis signaling to NF-κB activation, in a manner that requires caspase cleavage (as Casp8p43 is only present after caspase 8 activation), potentially as a homeostatic attempt of a dying cell to block its own death by initiating NF-κB driven activation of antiapoptotic regulatory proteins. Moreover, our hypothesis provides and explanation for prior observations [22]: Jurkat T cells stably transfected with HIV LTR-Luc were stimulated to die by ultraviolet (UV) irradiation and LTR driven luciferase expression measured. HIV transcription was induced by UV, and also was inhibited by a pan-caspase inhibitor (Z-VAD-Fmk), indicating that HIV LTR activation by UV requires caspase activation [22].…”

“…Moreover, our hypothesis provides and explanation for prior observations [22]: Jurkat T cells stably transfected with HIV LTR-Luc were stimulated to die by ultraviolet (UV) irradiation and LTR driven luciferase expression measured. HIV transcription was induced by UV, and also was inhibited by a pan-caspase inhibitor (Z-VAD-Fmk), indicating that HIV LTR activation by UV requires caspase activation [22]. Because UV irradiation causes apoptosis by activating a caspase 8 dependent death pathway [23], these data are consistent with our hypothesis that caspase 8 cleavage intermediates drive HIV replication.…”

Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

“…Furthermore, it is known that ionizing radiation is able to activate HIV promoter and gene expression in T cells. The gene expression of HIV viral infections are regulated by various cell signaling events that combine mitogens, cytokines, stress, and DNA damage (18). In other words, the enrichment of the HIV-infection and interferon gene sets in our data suggests a ‘communication network’ between DNA damage and central pathways in the immune response (Figs.…”