Kawanishi Y, Hayashi N, Katayama K, Ueda K, Takehara T, Miyoshi E, Mita E, Kasahara A, Fusamoto H, Kamada T
First Department of Medicine, Osaka University School of Medicine, Japan.
J Med Virol. 1995 Nov;47(3):272-7. doi: 10.1002/jmv.1890470314.
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.
利用HB611细胞研究了肿瘤坏死因子-α和/或干扰素-γ对乙型肝炎病毒复制的影响。这些细胞源自人肝母细胞瘤细胞Huh6，通过整合乙型肝炎病毒DNA而产生，并持续产生乙型肝炎病毒。每种细胞因子均能抑制细胞中乙型肝炎病毒的复制，以游离型乙型肝炎病毒DNA的量来评估，且不降低细胞活力。当两种细胞因子联合使用时，抑制作用更强。用1000 U/ml肿瘤坏死因子-α孵育细胞可使乙肝病毒DNA复制中间体减少55%，用1000 U/ml干扰素-γ孵育可使这些中间体减少51%。此外，用1000 U/ml肿瘤坏死因子-α和1000 U/ml干扰素-γ联合孵育可使乙肝病毒DNA复制中间体减少71%。相反，细胞因子并未明显降低乙型肝炎病毒RNA的量和乙型肝炎e抗原的分泌，且在上清液中未检测到2',5'-寡腺苷酸合成酶活性。这些结果表明，肿瘤坏死因子-α和干扰素-γ通过阻断逆转录的某些步骤来抑制乙型肝炎病毒复制，且2',5'-寡腺苷酸合成酶不参与这两种细胞因子抑制作用的潜在机制。
