Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein

Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein
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DOI:
10.1128/jvi.72.2.1043-1051.1998
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发表时间:
1998-02-01
影响因子:
5.4
通讯作者:
De Thé, H
De Thé, H
中科院分区:
医学2区
文献类型:
--
作者:
Chelbi-Alix, MK;Quignon, F;De Thé, H

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干扰素(IFN)诱导的早幼粒细胞白血病(PML)蛋白与核小体(NB)特异性相关,但其功能尚不清楚。两种NB相关蛋白PML和Sp100由IFN诱导。在这里,我们表明PML而不是Sp100的过表达会诱导对水泡性口炎病毒(VSV)(一种弹状病毒)和甲型流感病毒(一种正粘病毒)感染的抵抗力,但不会诱导对脑心肌炎病毒(一种小核糖核酸病毒)的抵抗力。病毒增殖的抑制依赖于PML表达水平和感染复数,并达到100倍。PML、Fas可干扰VSV mRNA和蛋白的合成,与IFN介导的MxA蛋白相比,PML的抗病毒活性较弱。虽然核小体定位的PML似乎并不需要的抗病毒效果,删除的PML卷曲螺旋结构域完全废除it. Taken在一起,这些结果表明,PML可以有助于在IFN-处理的细胞诱导的抗病毒状态。
The interferon (IFN)-induced promyelocytic leukemia (PML) protein is specifically associated with nuclear bodies (NBs) whose functions are yet unknown. Two of the NB-associated proteins, PML and Sp100, are induced by IFN. Here we show that overexpression of PML and not Sp100 induces resistance to infections by vesicular stomatitis virus (VSV) (a rhabdovirus) and influenza A virus (an orthomyxovirus) but not by encephalomyocarditis virus (a picornavirus). Inhibition of viral multiplication was dependent on both the level of PML expression and the multiplicity of infection and reached 100-fold. PML,Fas shown to interfere with VSV mRNA and protein synthesis, Compared to the IFN mediator MxA protein, PML had less powerful antiviral activity. While nuclear body localization of PML did not seem to be required for the antiviral effect, deletion of the PML coiled-coil domain completely abolished it. Taken together, these results suggest that PML can contribute to the antiviral state induced in IFN-treated cells.