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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\u2010\u03b1 decreased HBV DNA replicative intermediates by 55%, and that with 1, 000 U\/ml interferon\u2010\u03b3 decreased these by 51%. Furthermore, incubation with 1, 000 U\/ml tumor necrosis factor\u2010\u03b1 and 1, 000 U\/ml interferon\u2010\u03b3 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\u2032, 5\u2032\u2010oligoadenylate synthetase activity was not detected in the supernatant. These results suggest that tumor necrosis factor\u2010\u03b1 and interferon\u2010\u03b3 inhibit hepatitis B virus replication by blocking some step in reverse transcription and that the 2\u2032, 5\u2032\u2010oligoadenylate synthetase is not involved in the mechanism underlying the inhibition by these two cytokines. \u00a9 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jmv.1890470314","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T04:16:40Z","timestamp":1172895400000},"page":"272-277","source":"Crossref","is-referenced-by-count":13,"title":["Tumor necrosis factor\u2010\u03b1 and interferon\u2010\u03b3 inhibit synergistically viral replication in hepatitis B virus\u2010replicating 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