Cystamine inhibits human immunodeficiency virus-1 replication in cord blood-derived mononuclear phagocytes and lymphocytes.
The effects of cystamine on the human immunodeficiency virus (HIV-1) expression in cord blood monocytes-derived macrophages (CBMDM) and lymphocytes were investigated. Cystamine suppressed HIV-1 expression in CBMDM 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 adopted and fresh isolates) tested in the study. The addition of cystamine to cultures of HIV-1 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 indirect 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 synthesis as evaluated by trypan blue dye exclusion and [3H]-thymidine incorporation at doses of cystamine that inhibit the virus. HIV-1 infected CBMDM or lymphocyte cultures (without cystamine treatment) demonstrated giant syncytium formation or cytopathic effect (CPE), respectively, whereas cystamine-treated cultures lacked the giant syncytia or CPE induced by HIV-1 infection. Thus, these observations indicate that cystamine may have the potential to limit HIV-1 replication in monocytes/macrophages and lymphocytes in vivo and may represent a potentially useful compound in the treatment of pediatric HIV-1 infection and acquired immunodeficiency syndrome.
Ho
W Z
WZ
Division of Immunology and Infectious Diseases, Children's Hospital of Philadelphia 19104, USA.
Kaufman
D
D
Song
L
L
Cutillii
J R
JR
Douglas
S D
SD
D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003538:Cystamine / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015726:Giant Cells / Q000187:drug effects / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D008214:Lymphocytes / Q000821:virology*; D008264:Macrophages / Q000821:virology*; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D014764:Viral Proteins; D003538:Cystamine