Holm Geoffrey H, Zurney Jennifer, Tumilasci Vanessa, Leveille Simon, Danthi Pranav, Hiscott John, Sherry Barbara, Dermody Terence S
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-2581, USA.
J Biol Chem. 2007 Jul 27;282(30):21953-61. doi: 10.1074/jbc.M702112200. Epub 2007 May 31.
During viral infection, cells initiate antiviral responses to contain replication and inhibit virus spread. One protective mechanism involves activation of transcription factors interferon regulatory factor-3 (IRF-3) and NF-kappaB, resulting in secretion of the antiviral cytokine, interferon-beta. Another is induction of apoptosis, killing the host cell before virus disseminates. Mammalian reovirus induces both interferon-beta and apoptosis, raising the possibility that both pathways are initiated by a common cellular sensor. We show here that reovirus activates IRF-3 with kinetics that parallel the activation of NF-kappaB, a known mediator of reovirus-induced apoptosis. Activation of IRF-3 requires functional retinoic acid inducible gene-I and interferon-beta promoter stimulator-1, but these intracellular sensors are dispensable for activation of NF-kappaB. Interferon-beta promoter stimulator-1 and IRF-3 are required for efficient apoptosis following reovirus infection, suggesting a common mechanism of antiviral cytokine induction and activation of the cell death response.
在病毒感染期间，细胞会启动抗病毒反应以抑制病毒复制并阻止病毒传播。一种保护机制涉及转录因子干扰素调节因子3（IRF-3）和核因子κB（NF-κB）的激活，从而导致抗病毒细胞因子干扰素-β的分泌。另一种机制是诱导细胞凋亡，在病毒扩散之前杀死宿主细胞。哺乳动物呼肠孤病毒可诱导干扰素-β产生和细胞凋亡，这增加了两种途径均由共同的细胞感受器启动的可能性。我们在此表明，呼肠孤病毒激活IRF-3的动力学与已知的呼肠孤病毒诱导细胞凋亡的介质NF-κB的激活动力学相似。IRF-3的激活需要功能性视黄酸诱导基因-I和干扰素-β启动子刺激因子-1，但这些细胞内感受器对于NF-κB的激活并非必需。呼肠孤病毒感染后高效的细胞凋亡需要干扰素-β启动子刺激因子-1和IRF-3，这表明抗病毒细胞因子诱导和细胞死亡反应激活存在共同机制。
