Inhibition of HIV-1 productive infection in hepatoblastoma HepG2 cells by recombinant tumor necrosis factor-alpha.
OBJECTIVE
To evaluate the role of liver cells in and the effect of tumor necrosis factor-alpha (TNF-alpha) on HIV-1 replication.


METHODS
Human hepatoblastoma HepG2 cells were infected with various strains of HIV-1 and the effect of TNF-alpha treatment, either before or after infection, was monitored by p24 antigen assays. Northern blot analysis and gel retardation assays were performed to determine the expression of CD4 and HIV-1 trans-acting region (TAR)-binding proteins in these cells, respectively.


RESULTS
HepG2 cells are CD4+ and support active HIV-1 replication, producing infectious virions, as measured by both p24 production and ability to infect T-cell lines with the virus produced by HepG2 cells. In contrast to the stimulatory effect of TNF-alpha on HIV-1 replication in T-cells and monocytes, up to 200 U/ml TNF-alpha treatment, at various times, either before or after HIV-1 infection, substantially inhibited p24 antigen production in HepG2 cells without causing any remarkable cytotoxicity. Gel-retardation assay revealed enhancement of a DNA-binding protein in TNF-alpha-treated HepG2 cells that binds to a specific sequence of the HIV-1 TAR, compared with the untreated control.


CONCLUSIONS
These results indicate the importance of cellular factor(s) in HIV-1 infection and suggest that cytokines in different tissues can induce opposite effects. TAR-binding protein may act as an inhibitory factor for HIV-1 replication in the HepG2 cell line.
Banerjee
R
R
Department of Neoplastic Diseases, Mount Sinai School of Medicine, New York, New York 10029.
Sperber
K
K
Pizzella
T
T
Mayer
L
L
D015704:CD4 Antigens; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000382:microbiology*; D009000:Monocytes / Q000382:microbiology; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000382:microbiology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014771:Virion / Q000187:drug effects / Q000254:growth & development; D014779:Virus Replication / Q000187:drug effects*
D015704:CD4 Antigens; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha