Interferon alpha antagonizes the anti-hepatoma activity of the oncolytic virus M1 by stimulating anti-viral immunity
Interferon alpha antagonizes the anti-hepatoma activity of the oncolytic virus M1 by stimulating anti-viral immunity
复制标题
干扰素α通过刺激抗病毒免疫来拮抗溶瘤病毒M1的抗肝癌活性
DOI：
10.18632/oncotarget.15788
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发表时间：
2017-04-11
期刊：
影响因子：
--
通讯作者：
Liang, Peng
中科院分区：
文献类型：
--
作者：
Ying, Liu;Cheng, Hu;Liang, Peng
α病毒M1是一种靶向锌指抗病毒蛋白（ZAP）缺陷癌细胞的溶瘤病毒，可用于治疗肝细胞癌（HCC）。大多数HCC患者患有肝炎，需要长期抗病毒药物治疗。因此，有必要明确抗病毒药物是否影响M1的溶瘤作用。我们检测了用于治疗B/C型肝炎的药物在体外和体内对M1介导的溶瘤作用的影响。干扰素（IFN）-α诱导对M1病毒中度敏感的HCC细胞中抗病毒IFN刺激基因（ISGs）的表达。这导致M1的复制减少，并阻断M1介导的细胞凋亡。IFN-α的拮抗作用与ISGs的表达水平呈正相关。我们还检查了147例HCC患者。共有107例患者（73%）的肝组织中ZAP表达低于邻近组织。在这107例患者中，77%的患者为B型肝炎阳性，2%的患者为丙型肝炎阳性。对于ZAP低表达而ISGs中等表达的HBV或HCV感染患者应避免M1病毒和IFN联合使用。总之，本研究为接受溶瘤病毒M1治疗的患有B或C型肝炎的HCC患者的抗病毒治疗方案提供了依据。
Alpha virus M1 is an oncolytic virus that targets zinc-finger antiviral protein (ZAP)-defective cancer cells, and may be useful for treatment of hepatocellular carcinoma (HCC). Most of HCC patients have hepatitis and need long-term antiviral medication. Thus, it is necessary to clarify whether anti-virus medicines influence oncolytic effect of M1. We examined the effect of drugs used to treat hepatitis B/C on M1-mediated oncolysis in vitro and in vivo. Interferon (IFN)-α induces expression of antiviral IFN-stimulated genes (ISGs) in HCC cells with moderate sensitivity to M1 virus. This leads to reduced replication of M1, and blocking of M1-mediated apoptosis. The antagonistic effect of IFN-α is positively related with the expressive level of ISGs. We also examined a population of 147 HCC patients. A total of 107 patients (73%) had low ZAP expression in liver tissues relative to adjacent tissues. Among these 107 patients, 77% were positive for hepatitis B and 2% were positive for hepatitis C. A combination of M1 virus and IFN should be avoided in those patients with HBV or HCV infection, of who ZAP expression is low but ISGs expression is moderate. In conclusion, this study provides a basis for anti-viral regimens for HCC patients with hepatitis B or C who are given oncolytic virus M1.