5-azacytidine and 5-azadeoxycytidine inhibit human immunodeficiency virus type 1 replication in vitro.
Chemotherapeutic agents which affect the integration, stability, or inducibility of the human immunodeficiency virus (HIV) provirus would have considerable value in treating acquired immunodeficiency syndrome. Two nucleoside analogs of cytosine, 5-azacytidine and 5-azadeoxycytidine, which seem to have such value because of their capabilities to affect both the stability and the methylation patterns of the nucleic acids into which they are incorporated, were tested for their ability to inhibit the replication of HIV type 1 (HIV-1) in human CEM T cells in vitro. 5-Azadeoxycytidine (1 microM) completely inhibited HIV replication in CEM cells, by the criteria of reduced viral antigen expression and decreased supernatant reverse transcriptase activity, with little toxicity for the treated cells. 5-azacytidine (1 microM) also inhibited HIV replication, but less effectively. When added 2 or more h after CEM cells were infected with HIV-1, both 5-azacytosine derivatives were less effective than they were when added at the time of infection. Even 2 h of exposure to 5-azadeoxycytidine was sufficient for inhibition of HIV replication. Although long exposure to either analog at concentrations of 1 microM would result in pronounced cellular cytotoxicity, the the fact that short exposures to the same dose of drug inhibit HIV replication but are not toxic for the cells implies that cellular toxicity itself is not an important mechanism of the antiviral action of the analogs.
Institut National de la Recherche Scientifique-Santé, Université du Québec, Pointe-Claire, Canada.
J
J
Bouchard
M C
MC
Walker
J M
JM
Leclerc
N
N
Lapointe
R
R
Beaulieu
L
L
Thibodeau
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D000077209:Decitabine; D005455:Fluorescent Antibody Technique; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D014779:Virus Replication / Q000187:drug effects*
D000970:Antineoplastic Agents; D015704:CD4 Antigens; D000077209:Decitabine; D001374:Azacitidine