García María A, Collado Manuel, Muñoz-Fontela César, Matheu Ander, Marcos-Villar Laura, Arroyo Javier, Esteban Mariano, Serrano Manuel, Rivas Carmen
Centro Nacional de Biotecnología (CNB), Universidad Autónoma de Madrid, Madrid, Spain.
EMBO J. 2006 Sep 20;25(18):4284-92. doi: 10.1038/sj.emboj.7601302. Epub 2006 Sep 7.
Oncogenic viruses frequently target the pathways controlled by tumor suppressor genes, suggesting an extra function for these proteins as antiviral factors. The control exerted by the tumor suppressor Arf on cellular proliferation is crucial to restrict tumor development; however, a potential contribution of Arf to prevent viral infectivity has remained unexplored. In the present study, we investigated the consequences of loss or increased expression of Arf on viral infection. Our results reveal that ARF expression is induced by interferon and after viral infection. Furthermore, we show that ARF protects against viral infection in a gene dosage-dependent manner, and that this antiviral action is mediated in part by PKR through a mechanism that involves ARF-induced release of PKR from nucleophosmin complexes. Finally, Arf-null mice were hypersensitive to viral infection compared to wild-type mice. Together, our results reveal a novel and unexpected role for the tumor suppressor ARF in viral infection surveillance.
致癌病毒经常靶向由肿瘤抑制基因控制的通路，这表明这些蛋白质作为抗病毒因子具有额外功能。肿瘤抑制因子Arf对细胞增殖的控制对于限制肿瘤发展至关重要；然而，Arf在预防病毒感染方面的潜在作用仍未得到探索。在本研究中，我们研究了Arf缺失或表达增加对病毒感染的影响。我们的结果表明，ARF表达由干扰素诱导并在病毒感染后出现。此外，我们表明ARF以基因剂量依赖的方式保护细胞免受病毒感染，并且这种抗病毒作用部分由PKR介导，其机制涉及ARF诱导PKR从核磷蛋白复合物中释放。最后，与野生型小鼠相比，Arf基因缺失的小鼠对病毒感染高度敏感。总之，我们的结果揭示了肿瘤抑制因子ARF在病毒感染监测中具有意想不到的新作用。
