SELECTIVE EFFECTS OF DNA-DAMAGING AGENTS ON HIV LONG TERMINAL REPEAT ACTIVATION AND VIRUS-REPLICATION IN-VITRO

Much attention has recently focused on the observation that UV light c an activate the long terminal repeat (LTR) of the human immunodeficien cy virus (HIV). Although the mechanism of LTR activation remains obscu re, several lines of investigation have suggested that it is a result of activation of the NF-kappa B transcription factor(s) following sign aling events related to generalized DNA damage. In this report, we pre sent data demonstrating that HIV LTR activation is not a general conse quence of cellular DNA damage, but rather a process unique to specific genotoxic stimuli, and that it does not necessarily depend on activat ion of NF-kappa B. Furthermore, we demonstrate that several of these a gents can significantly increase HIV replication and accelerate CD4-po sitive lymphocyte cytotoxicity in vitro. These findings, therefore, co uld have clinical significance to AIDS patients with malignancies who are undergoing radiotherapy and chemotherapy.