HIV-1 EXPRESSION INDUCED BY ANTICANCER AGENTS IN LATENTLY HIV-1-INFECTED ACH2 CELLS

The expression of human immunodeficiency virus type 1 (HIV-1) in infec ted cells is induced (or enhanced) by a number of agents including pho rbol myristate acetate (PMA), phytohemagglutinin (PHA), certain infect ious agents, certain cytokines, and ultraviolet light. ACH2 cells repr esent 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 a rabinoside, and vinblastine potentiated the expression of HIV-1 in ACH 2 cells. There was no evidence of altered DNA methylation patterns in ACH2 cells cultured with 5-FU unlike with 5-AZC. The NF-KB binding act ivity 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 usi ng an oligonucleotide containing two NF-kappa B binding sites. These d ata suggest that the use of certain anti-cancer agents may induce (or enhance) the expression of HIV-1. (C) 1995 Academic Press, Inc.