Peltekian Cécile, Gordien Emmanuel, Garreau Florianne, Meas-Yedid Vannary, Soussan Patrick, Willams Virginie, Chaix Marie-Laure, Olivo-Marin Jean-Christophe, Bréchot Christian, Kremsdorf Dina
INSERM U370/Institut Pasteur, Faculté de Médecine Necker Enfants-Malades, 156, rue de Vaugirard, 75015 Paris, France.
J Hepatol. 2005 Dec;43(6):965-72. doi: 10.1016/j.jhep.2005.06.019. Epub 2005 Jul 14.
BACKGROUND/AIMS: The interferon (IFN) inducible MxA protein is endowed with antiviral activity against a broad range of RNA viruses. In a previous in vitro study, we demonstrated that MxA inhibits hepatitis B virus (HBV) replication, arguing that the antiviral activity of MxA is not restricted to RNA viruses but also includes a DNA virus. The aim of the present study was to further demonstrate in vivo the antiviral action of MxA against HBV.
We generated HBV and HBV/MxA transgenic mice lacking a functional IFN-alpha/beta receptor and thus constituting a good model to evaluate MxA-induced virus resistance. HBV proteins expression, viral load and HBV replication were compared in HBV and HBV/MxA mice.
An MxA-dependent moderate inhibitory effect on HBV expression was only observed in female HBV/MxA mice, in which MxA downregulates (i) viral HBeAg and capsid protein expression, (ii) viremia and (iii) HBV replication by decreasing the synthesis of HBV DNA replicative intermediates. Furthermore, these effects were not associated with changes to steady-state levels of HBV RNAs.
Our results show that in vivo, MxA is able per se to reduce HBV expression by a post-transcriptional mechanism, and thus participates in the antiviral activity of IFN-alpha against HBV.
背景/目的：干扰素（IFN）诱导的Mx A蛋白具有针对多种RNA病毒的抗病毒活性。在之前的一项体外研究中，我们证明Mx A抑制乙型肝炎病毒（HBV）复制，这表明Mx A的抗病毒活性不仅限于RNA病毒，还包括DNA病毒。本研究的目的是在体内进一步证明Mx A对HBV的抗病毒作用。
我们构建了缺乏功能性IFN-α/β受体的HBV和HBV/Mx A转基因小鼠，因此构成了评估Mx A诱导的病毒抗性的良好模型。比较了HBV和HBV/Mx A小鼠中HBV蛋白表达、病毒载量和HBV复制情况。
仅在雌性HBV/Mx A小鼠中观察到Mx A对HBV表达有中度抑制作用，其中Mx A通过降低HBV DNA复制中间体的合成来下调（i）病毒HBeAg和衣壳蛋白表达，（ii）病毒血症，以及（iii）HBV复制。此外，这些作用与HBV RNA稳态水平的变化无关。
我们的结果表明，在体内，Mx A本身能够通过转录后机制降低HBV表达，从而参与IFN-α对HBV的抗病毒活性。
