State Key Laboratory of Agrobiotechnology and College of Veterinary Medicine, China Agricultural University, Beijing, China.
Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, China.
PLoS Pathog. 2019 Jan 25;15(1):e1007559. doi: 10.1371/journal.ppat.1007559. eCollection 2019 Jan.
Type I interferon response plays a prominent role against viral infection, which is frequently disrupted by viruses. Here, we report Bcl-2 associated transcription factor 1 (Bclaf1) is degraded during the alphaherpesvirus Pseudorabies virus (PRV) and Herpes simplex virus type 1 (HSV-1) infections through the viral protein US3. We further reveal that Bclaf1 functions critically in type I interferon signaling. Knockdown or knockout of Bclaf1 in cells significantly impairs interferon-α (IFNα) -mediated gene transcription and viral inhibition against US3 deficient PRV and HSV-1. Mechanistically, Bclaf1 maintains a mechanism allowing STAT1 and STAT2 to be efficiently phosphorylated in response to IFNα, and more importantly, facilitates IFN-stimulated gene factor 3 (ISGF3) binding with IFN-stimulated response elements (ISRE) for efficient gene transcription by directly interacting with ISRE and STAT2. Our studies establish the importance of Bclaf1 in IFNα-induced antiviral immunity and in the control of viral infections.
I 型干扰素反应在对抗病毒感染中起着重要作用，而病毒经常会破坏这种反应。在这里，我们报告称，Bcl-2 相关转录因子 1（Bclaf1）在α疱疹病毒伪狂犬病病毒（PRV）和单纯疱疹病毒 1 型（HSV-1）感染过程中会通过病毒蛋白 US3 降解。我们进一步揭示 Bclaf1 在 I 型干扰素信号通路中起着关键作用。细胞中 Bclaf1 的敲低或敲除会显著损害干扰素-α（IFNα）介导的基因转录和针对缺乏 US3 的 PRV 和 HSV-1 的病毒抑制作用。在机制上，Bclaf1 维持了一种机制，允许 STAT1 和 STAT2 在受到 IFNα 刺激时有效地被磷酸化，更重要的是，通过直接与 ISRE 和 STAT2 相互作用，促进 IFN 刺激基因因子 3（ISGF3）与 IFN 刺激反应元件（ISRE）结合，从而有效地进行基因转录。我们的研究确立了 Bclaf1 在 IFNα 诱导的抗病毒免疫和控制病毒感染中的重要性。
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