L-2-oxothiazolidine-4-carboxylic acid inhibits human immunodeficiency virus type 1 replication in mononuclear phagocytes and lymphocytes.
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.
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The Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania Medical School, 19104, USA.
Starr
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Sison
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Douglas
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D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D010586:Phagocytes / Q000187:drug effects / Q000821:virology; D011247:Pregnancy; D011761:Pyrrolidonecarboxylic Acid; D013844:Thiazoles / Q000494:pharmacology* / Q000633:toxicity; D053778:Thiazolidines; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D013844:Thiazoles; D053778:Thiazolidines; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid