Pertussis toxin inhibits induction of human immunodeficiency virus type 1 in infected monocytes.
Tumor necrosis factor alpha (TNF-alpha) and 12-0-tetradecanoyl phorbol-13-acetate (TPA) activate human immunodeficiency virus type 1 (HIV-1) in U1 cells that are latently infected with HIV-1 to produce viral particles. Pertussis toxin, which inactivates several members of the G protein family of signaling components, including Gi, Go, and transducin, was found to inhibit either TPA or TNF-alpha induction of HIV-1 in U1 cells at the concentration of 1-10 ng/ml. Chloramphenicol acetyl transferase (CAT) assay revealed that pertussis toxin could inhibit HIV-1 gene expression. B-oligomer, the mitogenic and non-ADP-ribosylating component of pertussis toxin, did not show any effect on HIV-1 replication alone or in combination with TNF in the same concentration range. It was of particular interest to note that a single protein (Gi) with a molecular weight of 40 kDa was dose-dependently ADP-ribosylated after treatment with pertussis toxin in U1 cells. The degree of ADP ribosylation of Gi corresponded well to that of inhibition of HIV-1 upon treatment with pertussis toxin. These results strongly support the contention that TPA and TNF-alpha induction of HIV-1 is mediated by a Gi-like receptor-effector coupling protein in the membrane of U1 cells. On the basis of these findings, we propose a model for signal transduction of HIV-1 expression through c-kinase-dependent (TPA) and c-kinase-independent (TNF-alpha) pathways in the U1 cell to determine the point at which Gi-like protein is involved.
Chowdhury
I H
IH
Department of Microbiology, Tokyo Medical and Dental University, School of Medicine, Japan.
Koyanagi
Y
Y
Hazeki
O
O
Ui
M
M
Yamamoto
N
N
D002460:Cell Line; D019204:GTP-Binding Proteins / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D009000:Monocytes / Q000382:microbiology*; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D014775:Virus Activation / Q000187:drug effects*
D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate