HIV-1 expression induced by anti-cancer agents in latently HIV-1-infected ACH2 cells.
The expression of human immunodeficiency virus type 1 (HIV-1) in infected cells is induced (or enhanced) by a number of agents including phorbol myristate acetate (PMA), phytohemagglutinin (PHA), certain infectious agents, certain cytokines, and ultraviolet light. ACH2 cells represent latently HIV-1-infected T-cells, which produce only a low level of HIV-1 in vitro. We found that various anti-cancer agents including 5-azacytidine (5-AZC), 5-fluorouracil (5-FU), methotrexate, cytosine arabinoside, and vinblastine potentiated the expression of HIV-1 in ACH2 cells. There was no evidence of altered DNA methylation patterns in ACH2 cells cultured with 5-FU unlike with 5-AZC. The NF-kappa B binding activity was found to be enhanced in ACH2 cells exposed to 5-FU (but not in those exposed to 5-AZC) as assessed by the mobility shift assay using an oligonucleotide containing two NF-kappa B binding sites. These data suggest that the use of certain anti-cancer agents may induce (or enhance) the expression of HIV-1.
O'Brien
M C
MC
Experimental Retrovirology Section, National Cancer Institute, Bethesda, Maryland 20892.
Ueno
T
T
Jahan
N
N
Zajac-Kaye
M
M
Mitsuya
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002460:Cell Line; D002470:Cell Survival; D003561:Cytarabine / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology; D015497:HIV-1 / Q000254:growth & development*; D008727:Methotrexate / Q000494:pharmacology; D008745:Methylation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D016328:NF-kappa B; D010835:Phytohemagglutinins; D003561:Cytarabine; D014747:Vinblastine; D004247:DNA; D001374:Azacitidine; D013755:Tetradecanoylphorbol Acetate; D005472:Fluorouracil; D008727:Methotrexate