Research Papers:
Interferon alpha antagonizes the anti-hepatoma activity of the oncolytic virus M1 by stimulating anti-viral immunity
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Abstract
Liu Ying1,2,*, Hu Cheng3,*, Xu Wen Xiong1,2, Lin Yuan4, Zhang Hai Peng4, Zhong Wen Wen5, Liang Jian Ka4, Xiao Xiao6, Cai Jing4, Tan Ya Qian4, Gao Zhi Liang1,2, Yan Guang Mei4,7, Zhu Wen Bo4, Peng Liang1,2
1Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
2Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
3Department of Urology Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
4Department of Pharmacology, Sun Yat-Sen University, Guangzhou, China
5Department of Urology Diseases, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
6Department of Pharmacy, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
7Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
*These authors contributed equally to this work
Correspondence to:
Peng Liang, email: [email protected]
Zhu Wen Bo, email: [email protected]
Keywords: hepatocellular carcinoma, oncolytic virus M1 virus, interferon, interferon-stimulated genes, ZAP
Received: December 20, 2016 Accepted: February 15, 2017 Published: March 01, 2017
ABSTRACT
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.
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