Signal Transduction and HIV Transcriptional Activation After Exposure to Ultraviolet Light and Other DNA‐Damaging Agents

Abstract Short wavelength (254 nm) ultraviolet light (UVC)† radiation was much more potent in activating transcription of human immunodeficiency virus 1 (HIV) reporter genes stably integrated into the genomes of human and monkey cells than ionizing radiation (IR) from a 137 Cs source at similarly cytotoxic doses. A similar differential was also observed when c‐jun transcription levels were examined. However, these transcription levels do not correlate with activation of nuclear factor (NF)‐kB and AP‐1 measured by band‐shift assays., i. e. both types of radiation produce similar increases in NF‐kB and AP‐1 activity, suggesting existence of additional levels of regulation during these responses. Because of the well‐established involvement of cytoplasmic signaling pathways in the cellular response to tumor necrosis factor‐α (TNF‐α), UVC, and IR using other types of assays, the role of TNF‐α in the UVC response of HIV and c‐jun was investigated in our cell system. We demonstrate that UVC and TNF‐α activate HIV gene expression in a synergistic fashion, suggesting that it is unlikely that TNF‐α is involved in UVC activation of HIV transcription in stably transfected HeLa cells. Moreover, maximum TNF‐α stimulation resulted in one order of magnitude lower levels of HIV expression than that observed after UVC exposure. We also observed an additive effect of UVC and TNF‐α on c‐jun steady‐state mRNA levels, suggestive of a partial overlap in activation mechanism of c‐jun by UVC and TNF‐α; yet these responses are distinct to some extent. Our results indicate that the HIV, and to some extent also the c‐jun , transcriptional responses to UVC are not the result of TNF‐α stimulation and subsequent downstream cytoplasmic signaling events in HeLa cells. Additional levels of regulation that do not directly involve the NF‐kB and AP‐1 transcription factors, such as changes in chromatin structure associated with the UV repair process, may also be important for a full transcriptional response of HIV and c‐jun to UVC. In addition to the new data, this report also summarizes our current views regarding UVC‐induced activations of HIV gene expression in stably transfected cells.