Abstract
AimThe 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.MethodsHBV-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.ResultsAs 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.ConclusionsOur findings suggest that ZAP could inhibit HBV replication in vivo in mice, which offers a new target for anti-HBV drug development.
Highlights
Hepatitis B virus (HBV) infection is a serious global public health problem, and approximately two billion people who have been infected worldwide
The zinc finger antiviral protein (ZAP) transgenic mouse and HBV replication mouse model All mice used in this study were breeded at specificpathogen-free (SPF) level, weighing 22-24 g
The effect of ZAP on HBV transcription and replication In present study, the 3.5 kb mRNA and 2.4/2.1 kb mRNA of HBV were detected in both ZAP transgenic mouse and control mouse (Figure 1A)
Summary
Hepatitis B virus (HBV) infection is a serious global public health problem, and approximately two billion people who have been infected worldwide. 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]. How to effectively control and even eliminate virus replication has been concerned increasingly by clinicians [4,5]. Five oral nucleos(t)ide analogues (NAs) are approved for the treatment of chronic HBV infection [6,7,8], which decrease virus production by inhibiting the HBV DNA polymerase.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
