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Int J Med Sci 2018; 15(12):1356-1364. doi:10.7150/ijms.26125 This issue Cite

Research Paper

AGK2, A SIRT2 Inhibitor, Inhibits Hepatitis B Virus Replication In Vitro And In Vivo

Hai-Bo Yu, Hui Jiang, Sheng-Tao Cheng, Zhong-Wen Hu, Ji-Hua Ren✉, Juan Chen✉

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China

✉ Corresponding authors: Professor Juan Chen, Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Chongqing, 400016, P.R. China. Tel: (86)-02368818 More

Citation:
Yu HB, Jiang H, Cheng ST, Hu ZW, Ren JH, Chen J. AGK2, A SIRT2 Inhibitor, Inhibits Hepatitis B Virus Replication In Vitro And In Vivo. Int J Med Sci 2018; 15(12):1356-1364. doi:10.7150/ijms.26125. https://www.medsci.org/v15p1356.htm
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Abstract

Sirtuin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD +)-dependent class III histone deacetylase. We have reported that HBx (hepatitis B virus X protein)-elevated SIRT2 promotes HBV replication and hepatocarcinogenesis. However, the potential anti-HBV effect of AGK2, a selective inhibitor of SIRT2, has not been reported. Here, the role of AGK2 on HBV replication was examined in the HepAD38 and HepG2-NTCP cell lines. The HBV genome was stably integrated in HepAD38 cell line which expresses HBV under the control of tetracycline. The HepG2-NTCP cells expressing the sodium taurocholate cotransporting polypeptide (NTCP) receptor are susceptible to HBV infection. We found that AGK2 exhibited a robust anti-HBV activity with minimal hepatotoxicity. AGK2 inhibited the expression of HBV total and 3.5kb RNAs, DNA replicative intermediates and HBV core protein (HBc). Moreover, AGK2 treatment suppressed the secretion of the hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg). Importantly, AGK2 treatment inhibited serum HBV DNA, HBeAg and HBsAg levels as well as hepatic HBV DNA, RNA and HBc in the HBV transgenic mice. The results indicated that AGK2, as a SIRT2 inhibitor, might be a new therapeutic option for controlling HBV infection.

Keywords: AGK2, HBV, SIRT2

Citation styles

APA
Yu, H.B., Jiang, H., Cheng, S.T., Hu, Z.W., Ren, J.H., Chen, J. (2018). AGK2, A SIRT2 Inhibitor, Inhibits Hepatitis B Virus Replication In Vitro And In Vivo. International Journal of Medical Sciences, 15(12), 1356-1364. https://doi.org/10.7150/ijms.26125.

ACS
Yu, H.B.; Jiang, H.; Cheng, S.T.; Hu, Z.W.; Ren, J.H.; Chen, J. AGK2, A SIRT2 Inhibitor, Inhibits Hepatitis B Virus Replication In Vitro And In Vivo. Int. J. Med. Sci. 2018, 15 (12), 1356-1364. DOI: 10.7150/ijms.26125.

NLM
Yu HB, Jiang H, Cheng ST, Hu ZW, Ren JH, Chen J. AGK2, A SIRT2 Inhibitor, Inhibits Hepatitis B Virus Replication In Vitro And In Vivo. Int J Med Sci 2018; 15(12):1356-1364. doi:10.7150/ijms.26125. https://www.medsci.org/v15p1356.htm

CSE
Yu HB, Jiang H, Cheng ST, Hu ZW, Ren JH, Chen J. 2018. AGK2, A SIRT2 Inhibitor, Inhibits Hepatitis B Virus Replication In Vitro And In Vivo. Int J Med Sci. 15(12):1356-1364.

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