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Tumor necrosis factor‐α and interferon‐γ inhibit synergistically viral replication in hepatitis B virus‐replicating cells
Author(s) -
Kawanishi Yuko,
Hayashi Norio,
Katayama Kazuhiro,
Ueda Keiji,
Takehara Tetsuo,
Miyoshi Eiji,
Mita Eiji,
Kasahara Akinori,
Fusamoto Hideyuki,
Kamada Takenobu
Publication year - 1995
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.1890470314
Subject(s) - interferon , virology , biology , hepatitis b virus , tumor necrosis factor alpha , virus , viral replication , viral transformation , hepatoblastoma , cell culture , cytokine , microbiology and biotechnology , immunology , medicine , genetics
The effects of tumor necrosis factor‐a and/or interferon‐γ 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‐α decreased HBV DNA replicative intermediates by 55%, and that with 1, 000 U/ml interferon‐γ decreased these by 51%. Furthermore, incubation with 1, 000 U/ml tumor necrosis factor‐α and 1, 000 U/ml interferon‐γ 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‐α and interferon‐γ 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. © Wiley‐Liss, Inc.