INDUCTION OF RESISTANCE TO 1-BETA-D-ARABINOFURANOSYLCYTOSINE IN HUMANH9 CELL-LINE BY SIMIAN IMMUNODEFICIENCY VIRUS

We examined drug sensitivity of human T cell acute lymphoblastic leuke mia H9 cells chronically infected with simian immunodeficiency virus ( SIV mac) and found that the retrovirus-infected H9 cells showed 8.2-fo ld resistance to 1-beta-D-arabinofuranosylcytosine (Ara-C). In the inf ected cells, Ara-CTP levels decreased to 20% of that found in uninfect ed H9 cells after 3 h incubation at Ara-C concentration of 1 mu M, and 8.1-fold increase of cytidine deaminase activity was observed in the infected H9 cells. A competitive inhibitor of cytidine deaminase, 3, 4 , 5, 6-tetrahydrouridine (THU), at 100 mu M reversed Ara-C resistance in the infected cells. These results indicate that inducing increased cytidine deaminase activity by SIV mac infection conferred Ara-C resis tance to H9 cells. An understanding of these cellular differences in d rug sensitivity may aid in the development of therapeutic strategies a gainst retrovirus-infected cells. (C) 1995 Academic Press, Inc.