Cystamine inhibits HIV type 1 replication in cells of monocyte/macrophage and T cell lineages.
The effects of cysteamine (2-aminoethanethiol, MEA) and its disulfide, cystamine, on the human immunodeficiency virus (HIV-1) expression in chronically infected promonocytic cells (U1), T cell line (ACH-2), and peripheral blood monocyte-derived macrophages (MDM) were investigated. U1 and ACH-2 cells constitutively express low levels of virus, which is increased by the addition of tumor necrosis factor (TNF-alpha), interleukin 6 (IL-6), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and other inducers. Cystamine, in noncytotoxic doses, suppressed in a concentration-dependent fashion the induction of HIV-1 expression mediated by TNF-alpha, IL-6, GM-CSF, and monokine-enriched monocyte culture supernatants in both U1 and ACH-2 cells as determined by HIV-1 reverse transcriptase (RT) activity. Similarly, HIV-1 expression was substantially reduced in the cystamine-treated primary MDM cultures compared with the untreated control cultures. The addition of cystamine into HIV-1 chronically infected MDM (12 days after infection was established) also suppressed 80-90% of RT activity in comparison to the untreated controls. HIV-1 (Bal) infected MDM cultures (without cystamine treatment) demonstrated giant syncytium formation, whereas cystamine-treated cultures lacked the giant syncytia induced by HIV-1 infection. Cystamine also inhibited LPS-induced TNF production in MDM. In contrast to cystamine, cysteamine showed no significant effects on either the monokine-induced HIV-1 expression in U1 or ACH-2 or acute and chronic HIV-1 infection in MDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Ho
W Z
WZ
Division of Allergy, Immunology and Infectious Diseases, Children's Hospital of Philadelphia, University of Pennsylvania Medical School 19104, USA.
Zhu
X H
XH
Song
L
L
Lee
H R
HR
Cutilli
J R
JR
Douglas
S D
SD
D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D003538:Cystamine / Q000494:pharmacology*; D003543:Cysteamine / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D009000:Monocytes / Q000187:drug effects / Q000821:virology; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003543:Cysteamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003538:Cystamine