ISSN: 1838-7640Theranostics
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Theranostics 2020; 10(12):5600-5612. doi:10.7150/thno.44715 This issue Cite
Research Paper
Characterization of IL-21-expressing recombinant hepatitis B virus (HBV) as a therapeutic agent targeting persisting HBV infection
1. Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, People's Republic of China
2. Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Department of Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China
3. Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China
*These authors contributed equally to this work.
Citation:
Shen Z, Wu J, Gao Z, Wang J, Zhu H, Mao R, Wang X, Zhang J, Xie Y, Liu J. Characterization of IL-21-expressing recombinant hepatitis B virus (HBV) as a therapeutic agent targeting persisting HBV infection. Theranostics 2020; 10(12):5600-5612. doi:10.7150/thno.44715. https://www.thno.org/v10p5600.htm
Other stylesAbstract
Chronic infection by hepatitis B virus (HBV) is associated with high risks of liver fibrosis, cirrhosis and hepatocellular carcinoma. In mouse models of HBV persistence, interleukin 21 (IL-21) has been identified as a potent inducer of viral clearance. Strict hepatotropism makes recombinant HBV (rHBV) vectors ideal for liver-targeting gene delivery. Previously, we established an rHBV vector termed 5c3c, which is highly replicative by itself, but requires HBV envelope proteins provided in trans to produce virions. 5c3c-based rHBV virions are capable of delivering cargo gene expression driven by HBV Sp1 promoter into infected hepatocytes. In this work, we explore the feasibility of using 5c3c-derived rHBV for liver-specific delivery of IL-21 as treatment of chronic HBV infection.
Methods: 5c3c-derived rHBV replicons harboring mouse or human IL-21 genes (termed 5c3c-mIL-21 and 5c3c-hIL-21 respectively) were constructed and then tested for the production of rHBV virions in vitro and in vivo. 5c3c-mIL-21's anti-HBV effects were determined in chronic HBV mouse model. Furthermore, superinfection by rHBV virions was analysed using HBV-infected HepG2/NTCP cells and human liver chimeric mice.
Results: 5c3c-mIL-21 and 5c3c-hIL-21 were efficiently replicative and produced enveloped virions when provided with envelope proteins, both in vitro and in vivo. In mouse model of HBV persistence, IL-21 expressed from injected 5c3c-mIL-21 replicon induced complete viral clearance. 5c3c-mIL-21 and 5c3c-hIL-21 virions could infect HepG2/NTCP cells and engender sustained IL-21 expression. Most importantly, IL-21-expressing rHBV virions could superinfect HBV-infected HepG2/NTCP cells and human hepatocytes in human liver chimeric mice, and engender sustained IL-21 expression and rHBV production.
Conclusion: These data suggest the high potential of 5c3c-derived IL-21-expressing rHBV as a novel therapeutic against chronic HBV infection.
Keywords: hepatitis B virus, interleukin 21, recombinant HBV vector, superinfection, HBV clearance
Citation styles
APA
Shen, Z., Wu, J., Gao, Z., Wang, J., Zhu, H., Mao, R., Wang, X., Zhang, J., Xie, Y., Liu, J. (2020). Characterization of IL-21-expressing recombinant hepatitis B virus (HBV) as a therapeutic agent targeting persisting HBV infection. Theranostics, 10(12), 5600-5612. https://doi.org/10.7150/thno.44715.
ACS
Shen, Z.; Wu, J.; Gao, Z.; Wang, J.; Zhu, H.; Mao, R.; Wang, X.; Zhang, J.; Xie, Y.; Liu, J. Characterization of IL-21-expressing recombinant hepatitis B virus (HBV) as a therapeutic agent targeting persisting HBV infection. Theranostics 2020, 10 (12), 5600-5612. DOI: 10.7150/thno.44715.
NLM
Shen Z, Wu J, Gao Z, Wang J, Zhu H, Mao R, Wang X, Zhang J, Xie Y, Liu J. Characterization of IL-21-expressing recombinant hepatitis B virus (HBV) as a therapeutic agent targeting persisting HBV infection. Theranostics 2020; 10(12):5600-5612. doi:10.7150/thno.44715. https://www.thno.org/v10p5600.htm
CSE
Shen Z, Wu J, Gao Z, Wang J, Zhu H, Mao R, Wang X, Zhang J, Xie Y, Liu J. 2020. Characterization of IL-21-expressing recombinant hepatitis B virus (HBV) as a therapeutic agent targeting persisting HBV infection. Theranostics. 10(12):5600-5612.
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