Cystamine inhibits human immunodeficiency virus-1 replication in cord
blood-derived mononuclear phagocytes and lymphocytes
WZ Ho, D Kaufman, L Song, JR Cutillii and SD Douglas
Division of Immunology and Infectious Diseases, Children's Hospital of
Philadelphia 19104, USA.
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.
Volume 88,
Issue 3,
pp. 928-933,
08/01/1996
Copyright © 1996 by The American Society of Hematology