Tumor necrosis factor-alpha and interferon-gamma inhibit synergistically viral replication in hepatitis B virus-replicating cells.
The effects of tumor necrosis factor-alpha and/or interferon-gamma on the replication of hepatitis B virus were examined using HB611 cells. These cells were derived from human hepatoblastoma cells, Huh6, by integrating hepatitis B virus DNA, and produce hepatitis B virus continuously. Each of the cytokines inhibited hepatitis B virus replication in the cells assessed as the amount of episomal hepatitis B virus DNA, without a decrease in cell viability. When the two cytokines were administered together, the inhibitory effect became greater. Incubation of the cells with 1,000 U/ml tumor necrosis factor-alpha decreased HBV DNA replicative intermediates by 55%, and that with 1,000 U/ml interferon-gamma decreased these by 51%. Furthermore, incubation with 1,000 U/ml tumor necrosis factor-alpha and 1,000 U/ml interferon-gamma in combination decreased HBV DNA replicative intermediates by 71%. In contrast, the amount of hepatitis B virus RNA and secretion of hepatitis B e antigen were not apparently reduced by the cytokines, and 2',5'-oligoadenylate synthetase activity was not detected in the supernatant. These results suggest that tumor necrosis factor-alpha and interferon-gamma inhibit hepatitis B virus replication by blocking some step in reverse transcription and that the 2',5'-oligoadenylate synthetase is not involved in the mechanism underlying the inhibition by these two cytokines.
Kawanishi
Y
Y
First Department of Medicine, Osaka University School of Medicine, Japan.
Hayashi
N
N
Katayama
K
K
Ueda
K
K
Takehara
T
T
Miyoshi
E
E
Mita
E
E
Kasahara
A
A
Fusamoto
H
H
Kamada
T
T
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002461:Cell Line, Transformed; D004279:DNA, Viral / Q000032:analysis / Q000187:drug effects; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D012367:RNA, Viral / Q000032:analysis / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D000509:alpha-Fetoproteins / Q000378:metabolism
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D000509:alpha-Fetoproteins; D015088:2',5'-Oligoadenylate Synthetase