L-2-oxothiazolidine-4-carboxylic acid inhibits human immunodeficiency virus type 1 replication in mononuclear phagocytes and lymphocytes

Abstract

We investigated the effects of L-2-oxothiazolidine-4-carboxylic acid (OTC; Procysteine), a cysteine prodrug, on human immunodeficiency virus type 1 (HIV-1) expression in both adult peripheral and cord blood mononuclear phagocytes and lymphocytes. OTC suppressed HIV-1 expression in monocyte-derived macrophages (MDM) and lymphocytes in a dose-dependent fashion as determined by HIV-1 reverse transcriptase (RT) activity. This inhibitory effect of OTC occurred with three HIV-1 strains (two laboratory-adapted strains and one primary isolate). Addition of OTC to chronically HIV-1-infected MDM cultures also suppressed RT activity by 40 to 50% in comparison to untreated controls. The inhibitory effects of OTC on HIV-1 were not caused by toxicity to MDM or lymphocytes because there was no change in cell viability or cellular DNA synthesis, as evaluated by trypan blue dye exclusion and [3H]thymidine incorporation, at doses of OTC that inhibit virus replication. These observations indicate that OTC has the potential to limit HIV-1 replication in mononuclear phagocytes and lymphocytes and may be useful in the treatment of HIV-1 infection and AIDS.