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磷脂翻转酶 1 体外和体内抑制乙型肝炎病毒复制。

Inhibition of Hepatitis B virus replication by phospholipid scramblase 1 in vitro and in vivo.

机构信息

Beijing Institute of Radiation Medicine, PR China.

出版信息

Antiviral Res. 2012 Apr;94(1):9-17. doi: 10.1016/j.antiviral.2012.01.010. Epub 2012 Feb 9.

DOI:10.1016/j.antiviral.2012.01.010
PMID:22342889
Abstract

Human Phospholipid scramblase 1 (PLSCR1) is an α/β interferon-inducible protein that mediates antiviral activity against RNA viruses including vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV). In the present study, we investigated the antiviral activity of PLSCR1 protein against HBV (Hepatitis B virus). Firstly, PLSCR1 mRNA and protein expression was found to be downregulated in HepG2 cells after HBV infection. Then by performing co-transient-transfection experiments in cells and hydrodynamics-based transfection experiments in mice using a HBV expression plasmid and a PLSCR1 expression plasmid, we found that PLSCR1 inhibited HBV replication in vitro and in vivo through a significant reduction in the synthesis of viral proteins, DNA replicative intermediates and HBV RNAs. We also demonstrated that the antiviral action of PLSCR1 against HBV occurs, partly at least, by activating the Jak/Stat pathway. In conclusion, our results suggest that the expression of PLSCR1 is involved in HBV replication and that PLSCR1 has antiviral activity against HBV.

摘要

人源磷脂 scramblase 1(PLSCR1)是一种 α/β 干扰素诱导的蛋白,可介导针对包括水疱性口炎病毒(VSV)和脑心肌炎病毒(EMCV)在内的 RNA 病毒的抗病毒活性。在本研究中,我们研究了 PLSCR1 蛋白对乙型肝炎病毒(HBV)的抗病毒活性。首先,在 HBV 感染后,发现 HepG2 细胞中的 PLSCR1 mRNA 和蛋白表达下调。然后,通过在细胞中进行共瞬时转染实验和在小鼠中进行基于水力的转染实验,使用 HBV 表达质粒和 PLSCR1 表达质粒,我们发现 PLSCR1 通过显著减少病毒蛋白、DNA 复制中间体和 HBV RNA 的合成,在体外和体内抑制 HBV 复制。我们还表明,PLSCR1 对 HBV 的抗病毒作用至少部分是通过激活 Jak/Stat 途径发生的。总之,我们的结果表明 PLSCR1 的表达参与了 HBV 的复制,并且 PLSCR1 对 HBV 具有抗病毒活性。

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