Antiviral activity of limitin against encephalomyocarditis virus, herpes simplex virus, and mouse hepatitis virus: Diverse requirements by limitin and alpha interferon for interferon regulatory factor 1
Antiviral activity of limitin against encephalomyocarditis virus, herpes simplex virus, and mouse hepatitis virus: Diverse requirements by limitin and alpha interferon for interferon regulatory factor 1
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DOI：
10.1128/jvi.77.17.9622-9631.2003
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发表时间：
2003-09-01
影响因子：
5.4
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Kawamoto, SI;Oritani, K;Matsuzawa, Y
limittin与α干扰素（ifn - α）和ifn - β具有序列同源性，并利用ifn - α / β受体。然而，它对正常髓系和红系祖细胞的增殖没有影响。在这项研究中，我们表明，限制在体外和体内抗病毒活性。限制素不仅抑制1型脑心肌炎病毒或单纯疱疹病毒（HSV）感染的L929细胞的细胞病变作用，而且抑制2型肝炎病毒（MHV）感染的DBT细胞的斑块形成。此外，给药限制小鼠抑制mhv诱导的肝炎和单纯疱疹病毒诱导的死亡。抗病毒活性可能部分由2',5'-寡聚腺苷酸合成酶、rna依赖性蛋白激酶和Mx蛋白介导，它们抑制病毒复制或降解病毒成分，因为限药蛋白诱导了它们的mRNA表达和酶活性。虽然限药素在体外具有与IFN-et一样强的抗病毒活性（提供50%细胞病变抑制作用的浓度类似于30 pg/ml），但对IFN调节因子1 （IRF-1）诱导抗病毒状态的依赖性在限药素和IFN- α中是不同的。在irf -1缺陷的成纤维细胞中，需要比ifn - α更高浓度的限制才能诱导抗病毒活性和ifn刺激反应元件蛋白的转录。骨髓抑制的独特信号和较少的特性表明，人类同源物可能被用作一种新的抗病毒药物。
Limitin has sequence homology with alpha interferon (IFN-alpha) and IFN-beta and utilizes the IFN-alpha/beta receptor. However, it has no influence on the proliferation of normal myeloid and erythroid progenitors. In this study, we show that limitin has antiviral activity in vitro as well as in vivo. Limitin inhibited not only cytopathic effects in encephalomyocarditis virus- or herpes simplex virus (HSV) type 1-infected L929 cells, but also plaque formation in mouse hepatitis virus (MHV) type 2-infected DBT cells. In addition, administration of limitin to mice suppressed MHV-induced hepatitis and HSV-induced death. The antiviral activity may be mediated in part by 2',5'-oligoadenylate synthetase, RNA-dependent protein kinase, and Mx protein, which inhibit viral replication or degrade viral components, because limitin induced their mRNA expression and enzyme activity. While limitin has antiviral activity as strong as that of IFN-et in vitro (the concentration that provided 50% inhibition of cytopathic effect is similar to30 pg/ml), IFN regulatory factor 1 (IRF-1) dependencies for induction of an antiviral state were different for limitin and IFN-alpha. In IRF-1-deficient fibroblasts, a higher concentration of limitin than of IFN-alpha was required for the induction of antiviral activity and the transcription of proteins from IFN-stimulated response element. The unique signals and the fewer properties of myelosuppression suggest that a human homolog of limitin may be used as a new antiviral drug.