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. 2015 Feb 13;12:25.
doi: 10.1186/s12985-015-0245-0.

The Efficacy of Zinc Finger Antiviral Protein Against Hepatitis B Virus Transcription and Replication in Tansgenic Mouse Model

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Free PMC article

The Efficacy of Zinc Finger Antiviral Protein Against Hepatitis B Virus Transcription and Replication in Tansgenic Mouse Model

En-Qiang Chen et al. Virol J. .
Free PMC article

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.

Figures

Figure 1
Figure 1
The transcription levels of HBV RNA in mouse liver tissue. (A): Lanes 1-5 for ICR control mouse and lanes 6-10 for ZAP transgenic mouse. (B): Quantitative analysis results of the 3.5-kb HBV mRNA. (C): Quantitative analysis results of the 2.4/2.1-kb HBV mRNA. The mean value of ICR control mouse was defined as 1, and GAPDH was used as internal control.
Figure 2
Figure 2
The replication levels of HBV DNA in mouse liver tissue. (A): Lanes 1-5 for ICR mice and lanes 6-10 for ZAP transgenic mouse. (B): Quantitative analysis results of the relative intensity of HBV DNA replication intermediates. The mean value of ICR control mouse was set to 1.
Figure 3
Figure 3
Immunohistochemical staining of HBsAg (A-D) and HBcAg (E-H) in liver tissue sections.

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