Feigenblum D, Walker R, Schneider R J
Department of Biochemistry and Microbiology, Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
J Virol. 1998 Nov;72(11):9257-66. doi: 10.1128/JVI.72.11.9257-9266.1998.
Virus infection of animal cells can induce intracellular antiviral responses mediated by the induction of interferon-regulatory transcription factors (IRFs), which bind to and control genes directed by the interferon-stimulated response element (ISRE). The purpose of this study was to determine whether adenovirus (Ad) induces IRFs during infection, because they might play a role in promoting viral pathogenesis. Here we show that after the late phase of infection, Ad induces a transcription factor related to the IRF family of factors. The IRF is induced shortly after Ad entry into late phase and is shown to stimulate ISRE-directed transcription, to require activation by protein tyrosine kinase signalling, and to be induced several hours prior to the inhibition of cell protein synthesis. Inhibition of tyrosine kinase activity blocks Ad induction and activation of the IRF. Attempts to identify the Ad-induced factor immunologically and by photo-UV cross-linking indicate that it is likely a novel member of the IRF family. Finally, several independent lines of evidence also suggest that Ad induction of the IRF might correlate with the ability of the virus to block host cell protein synthesis later during infection.
动物细胞的病毒感染可通过诱导干扰素调节转录因子(IRF)介导细胞内抗病毒反应,这些转录因子与干扰素刺激反应元件(ISRE)指导的基因结合并对其进行调控。本研究的目的是确定腺病毒(Ad)在感染过程中是否诱导IRF,因为它们可能在促进病毒发病机制中发挥作用。在此我们表明,在感染后期,Ad诱导一种与IRF家族因子相关的转录因子。该IRF在Ad进入后期后不久被诱导,显示出可刺激ISRE指导的转录,需要蛋白酪氨酸激酶信号传导激活,并且在抑制细胞蛋白质合成前数小时被诱导。抑制酪氨酸激酶活性可阻断Ad对IRF的诱导和激活。通过免疫和光UV交联鉴定Ad诱导因子的尝试表明,它可能是IRF家族的一个新成员。最后,几条独立的证据线索还表明,Ad对IRF的诱导可能与病毒在感染后期阻断宿主细胞蛋白质合成的能力相关。