CYSTAMINE INHIBITS HUMAN IMMUNODEFICIENCY VIRUS-1 REPLICATION IN CORDBLOOD-DERIVED MONONUCLEAR PHAGOCYTES AND LYMPHOCYTES

The effects of cystamine on the human immunodeficiency virus (HIV-1) e xpression in cord blood monocytes-derived macrophages (CBMDM) and lymp hocytes were investigated. Cystamine suppressed HIV-1 expression in CB MDM and lymphocytes in a concentration-dependent fashion as determined by HIV-1 reverse transcriptase (RT) activity. This inhibitory effect of cystamine occurred with all five HIV-1 strains (both laboratory ado pted and fresh isolates) tested in the study, The addition of cystamin e to cultures of HIV-I chronically infected CBMDM also suppressed 80% to 90% of RT activity in comparison with untreated controls. Cystamine also decreased HIV-1 protein expression in CBMDM as determined by ind irect immunofluorescence assay, The inhibitory effects of cystamine on HIV-1 did not appear to be caused by toxicity to CBMDM or lymphocytes because there was no change in cell viability or cellular DNA synthes is as evaluated by trypan blue dye exclusion and [H-3]-thymidine incor poration at doses of cystamine that inhibit the virus, HIV-1 infected CBMDM or lymphocyte cultures (without cystamine treatment) demonstrate d giant syncytium formation or cytopathic effect (CPE), respectively, whereas cystamine-treated cultures lacked the giant syncytia or CPE in duced by HIV-1 infection. Thus, these observations indicate that cysta mine may have the potential to limit HIV-1 replication in monocytes/ma crophages and lymphocytes in vivo and may represent a potentially usef ul compound in the treatment of pediatric HIV-1 infection and acquired immunodeficiency syndrome, (C) 1996 by The American Society of Hemato logy.