Rajan P, Swaminathan S, Zhu J, Cole C N, Barber G, Tevethia M J, Thimmapaya B
Robert H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611.
J Virol. 1995 Feb;69(2):785-95. doi: 10.1128/JVI.69.2.785-795.1995.
Cells use the interferon-induced, double-stranded-RNA-dependent protein kinase PKR as a defense against virus infections. Upon activation, PKR phosphorylates and thereby inactivates the protein synthesis initiation factor eIF-2, resulting in the cessation of protein synthesis. Viruses have evolved various strategies to counteract this cellular defense. In this paper, we show that simian virus 40 (SV40) large-T antigen can antagonize the translational inhibitory effect resulting from the activation of PKR in virus-infected cells. Unlike the situation with other virus-host cell interactions, SV40 large-T antigen does not block the activation of PKR, suggesting that SV40 counteracts the cellular antiviral response mediated by PKR at a step downstream of PKR activation. Mutational analysis of large-T antigen indicates that a domain located between amino acids 400 and 600 of large-T antigen is responsible for this function. These results define a novel translational regulatory function for the SV40 large-T antigen.
细胞利用干扰素诱导的双链RNA依赖性蛋白激酶PKR作为抵御病毒感染的防御机制。激活后，PKR使蛋白质合成起始因子eIF-2磷酸化并使其失活，导致蛋白质合成停止。病毒已经进化出各种策略来对抗这种细胞防御。在本文中，我们表明猿猴病毒40（SV40）大T抗原可以拮抗病毒感染细胞中PKR激活所产生的翻译抑制作用。与其他病毒-宿主细胞相互作用的情况不同，SV40大T抗原不会阻断PKR的激活，这表明SV40在PKR激活的下游步骤中对抗由PKR介导的细胞抗病毒反应。对大T抗原的突变分析表明，大T抗原位于氨基酸400至600之间的结构域负责此功能。这些结果定义了SV40大T抗原的一种新的翻译调节功能。
