The efficacy of zinc finger antiviral protein against hepatitis B virus transcription and replication in tansgenic mouse
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RESEARCH
Open Access
The efficacy of zinc finger antiviral protein against hepatitis B virus transcription and replication in tansgenic mouse model En-Qiang Chen1,2, Jie Dai1,2, Lang Bai1,2 and Hong Tang1,2*
Abstract Aim: The zinc finger antiviral protein (ZAP) is a mammalian host restriction factor, and it could inhibit HBV RNA synthesis in vitro experiments. However, the role of ZAP against HBV in vivo environment is unclear. This study aimed to investigate whether ZAP could act against HBV transcription and replication in ZAP tansgenic mouse model. Methods: HBV-replication-competent plasmid pHBV4.1 was transferred to ZAP transgenic ICR mouse via the tail vein using a hydrodynamic in vivo transfection procedure, and ICR mouse were used as controls. HBV RNA and HBV DNA replication intermediates in the liver were respectively analyzed by Northern blotting and Southern blotting. The expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the liver tissue was detected by immunohistochemical staining. Results: As compared to ICR control mouse, the levels of 3.5 kb mRNA in ZAP transgenic mouse were decreased by 8.4%; while the level of HBV DNA replication intermediates was decreased by 82%. In addition, the expression of HBsAg and HBcAg in ZAP transgenic mouse liver were both significantly less than that of ICR control mouse. Conclusions: Our findings suggest that ZAP could inhibit HBV replication in vivo in mice, which offers a new target for anti-HBV drug development. Keywords: Zinc-finger antiviral protein, Hepatitis B virus, Transgenic mouse, Transcription and replication
Background Hepatitis B virus (HBV) infection is a serious global public health problem, and approximately two billion people who have been infected worldwide. Of them, there are more than 350 million who are chronic carriers of HBV [1,2]. Sufficient evidences have showed that the level of serum HBV DNA is a strong predictor of HBV-related complications [3]. And how to effectively control and even eliminate virus replication has been concerned increasingly by clinicians [4,5]. In past decades, five oral nucleos(t)ide analogues (NAs) are approved for the treatment of chronic HBV infection [6-8], which decrease virus production by inhibiting the HBV DNA polymerase. However, because of the * Correspondence: [email protected] 1 Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China 2 Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
persistence of HBV covalently closed circular (cccDNA) in liver, current NAs treatment rarely eradicate HBV infection, and most patients require long-term NAs administration. Recently, with the extension of duration of treatment, the issues of drug resistance, viral relapse and particularly suboptimal response to current antiviral agents are increasingly evident [9-12], and how to manage those patients after initial therapy failure has become the primary concern for clinicians [5].
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