The p59 oligoadenylate synthetase-like protein possesses antiviral activity that requires the C-terminal ubiquitin-like domain

The p59 oligoadenylate synthetase-like protein possesses antiviral activity that requires the C-terminal ubiquitin-like domain
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DOI:
10.1099/vir.0.2008/003558-0
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发表时间:
2008-11-01
影响因子:
3.8
通讯作者:
Hartmann, Rune
Hartmann, Rune
中科院分区:
医学3区
文献类型:
--
作者:
Marques, Joao;Anwar, Jangawar;Hartmann, Rune

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病毒感染哺乳动物细胞促使先天免疫系统启动抗病毒反应。对病毒的识别触发了几种抗病毒信号通路,其中包括2‘-5’低聚腺苷酸合成酶(OAS)蛋白家族。由OAS样(OASL)基因编码的p59蛋白是OAS家族的非典型成员,因为它缺乏典型的2‘-5’低聚腺苷酸合成酶活性。我们决定通过在Vero细胞中异位表达p59蛋白,然后用病毒感染这些细胞来研究p59可能的抗病毒活性。我们证明OASL对单链RNA病毒小核糖核酸病毒、脑心肌炎病毒有抗病毒作用,但对大型DNA病毒、单纯疱疹病毒1没有抗病毒作用。重要的是,这种抗病毒活性在缺乏p59泛素样c端结构域的p59的截断版本中丢失。综上所述,我们的研究结果表明p59确实是一种抗病毒蛋白,通过一种不同于其他OAS蛋白的新机制起作用。
Viral infection of mammalian cells prompts the innate immune system to initiate an antiviral response. The recognition of the virus triggers several antiviral signalling pathways, which among others include the family of 2'-5' oligoadenylate synthetase (OAS) proteins. The p59 protein encoded by the OAS-like (OASL) gene is an atypical member of the OAS family in the sense that it lacks the characteristic 2'-5' oligoadenylate synthetase activity. We decided to investigate the putative antiviral activity of p59 by ectopically expressing this protein in Vero cells and then infecting these cells with virus. We demonstrate that OASL has an antiviral effect against the single-stranded RNA virus picornavirus, encephalomyocarditis virus, but not against a large DNA virus, herpes simplex virus 1. Importantly, this antiviral activity was lost in a truncated version of p59 lacking the ubiquitin-like C-terminal domain of p59. Taken together our results indicate that p59 is indeed an antiviral protein that works through a novel mechanism distinct from other OAS proteins.