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 can activate the long terminal repeat (LTR) of the human immunodeficiency virus (HIV). Although the mechanism of LTR activation remains obscure, several lines of investigation have suggested that it is a result of activation of the NF-kappa B transcription factor(s) following signaling events related to generalized DNA damage. In this report, we present data demonstrating that HIV LTR activation is not a general consequence of cellular DNA damage, but rather a process unique to specific genotoxic stimuli, and that it does not necessarily depend on activation of NF-kappa B. Furthermore, we demonstrate that several of these agents can significantly increase HIV replication and accelerate CD4-positive lymphocyte cytotoxicity in vitro. These findings, therefore, could have clinical significance to AIDS patients with malignancies who are undergoing radiotherapy and chemotherapy.
Manome
Y
Y
Division of Cancer Pharmacology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Yao
X J
XJ
Kufe
D W
DW
Cohen
E A
EA
Fine
H A
HA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000528:radiation effects / Q000821:virology; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004279:DNA, Viral / Q000187:drug effects* / Q000528:radiation effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000528:radiation effects; D016325:HIV Long Terminal Repeat / Q000187:drug effects* / Q000528:radiation effects; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells / Q000187:drug effects / Q000528:radiation effects / Q000821:virology; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis; D014466:Ultraviolet Rays; D014775:Virus Activation / Q000187:drug effects / Q000528:radiation effects; D014779:Virus Replication / Q000187:drug effects / Q000528:radiation effects
D000970:Antineoplastic Agents; D004279:DNA, Viral; D016328:NF-kappa B