A PLATELET-ACTIVATING-FACTOR ANTAGONIST, RP-55778, INHIBITS CYTOKINE-DEPENDENT INDUCTION OF HUMAN-IMMUNODEFICIENCY-VIRUS EXPRESSION IN CHRONICALLY INFECTED PROMONOCYTIC CELLS

A platelet-activating factor antagonist,. RP 55778, potently suppressed the induction of human immunodeficiency virus (HIV) expression in chronically infected promonocytic U1 cells. RP 55778 inhibited the production of reverse transcriptase activity in U1 cells stimulated with the transcriptionally active inducers of virus production, tumor necrosis factor alpha and phorbol 12-myristate 13-acetate. This effect was correlated only in part with a reduction in the levels of HIV RNA, suggesting that this agent was also affecting posttranscriptional levels of virus production. In this regard, RP 55778 effectively blocked the induction of HIV expression in U1 cells stimulated with interleukin 6 and granulocyte-macrophage colony-stimulating factor, which act predominantly as posttranscriptional activators of HIV expression. Finally, RP 55778 inhibited the production of endogenous tumor necrosis factor a in phorbol 12-myristate 13-acetate-stimulated cells, thereby interfering with an autocrine pathway of virus expression. The suppressive effects of RP 55778 on HIV expression appeared to be independent of the platelet-activating factor cell surface receptor on U1 cells. RP 55778 inhibited acute HIV replication in primary T-cell blasts and the proliferative capacity of these cells. This study suggests that RP 55778 may represent potentially useful compounds in the treatment of HIV infection.