PT - JOURNAL ARTICLE AU - Dirk Daelemans AU - Jose A. Esté AU - Myriam Witvrouw AU - Christophe Pannecouque AU - Heidi Jonckheere AU - Stefano Aquaro AU - Carlo-Federico Perno AU - Erik De Clercq AU - Anne-Mieke Vandamme TI - <em>S</em> <strong>-</strong>Adenosylhomocysteine Hydrolase Inhibitors Interfere with the Replication of Human Immunodeficiency Virus Type 1 through Inhibition of the LTR Transactivation AID - 10.1124/mol.52.6.1157 DP - 1997 Dec 01 TA - Molecular Pharmacology PG - 1157--1163 VI - 52 IP - 6 4099 - http://molpharm.aspetjournals.org/content/52/6/1157.short 4100 - http://molpharm.aspetjournals.org/content/52/6/1157.full SO - Mol Pharmacol1997 Dec 01; 52 AB - Various analogues of adenosine have been described as inhibitors ofS-adenosylhomocysteine (AdoHcy) hydrolase, and some of these AdoHcy hydrolase inhibitors (e.g., 3-deazaadenosine, 3-deazaaristeromycin, and 3-deazaneplanocin A) have also been reported to inhibit the replication of human immunodeficiency virus type 1 (HIV-1). When evaluated against HIV-1 replication in MT-4 cells, macrophages, or phytohemagglutinin-stimulated peripheral blood lymphocytes infected acutely or chronically with HIV-1IIIBor HIVBaL strains, a wide range of adenosine analogues did not inhibit HIV-1IIIB replication for 50% at subtoxic concentrations. However, they inhibited HIV-1 replication in HeLa CD4+ LTR-LacZ cells at concentrations well below cytotoxicity threshold. A close correlation was found among the inhibitory effect of the compounds on AdoHcy hydrolase activity, their inhibition of HIV-1 replication in Hela CD4+ LTR-LacZ cells, and their inhibition of the HIV-1 Tat-dependent and -independent transactivation of the long terminal repeat, whereas no inhibitory effect was seen on HIV-1 reverse transcription or a Tat-independent cytomegalovirus promoter. Our results suggest that AdoHcy hydrolase and the associated S-adenosylmethionine-dependent methylation mechanism play a role in the process of long terminal repeat transactivation and, hence, HIV replication.