Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Department of Medicine, Washington University School of Medicine, St Louis, Missouri, USA.
J Infect Dis. 2023 Nov 15;228(Suppl 7):S514-S521. doi: 10.1093/infdis/jiad325.
Ebola virus (EBOV) is a highly pathogenic virus that encodes 7 multifunctional structural proteins. Multiple host factors have been reported to interact with the EBOV proteins. Here, we found that tripartite motif-containing 14 (TRIM14), an interferon-stimulated gene that mediates cellular signaling pathways associated with type I interferon and inflammatory cytokine production, interacts with EBOV nucleoprotein to enhance interferon-β (IFN-β) and nuclear factor-κB (NF-κB) promotor activation. Moreover, TRIM14 overexpression reduced viral replication in an infectious but biologically contained EBOVΔVP30 system by approximately 10-fold without affecting viral protein expression. Furthermore, TRM14-deficient mice were more susceptible to mouse-adapted EBOV infection than wild-type mice. Our data suggest that TRIM14 is a host factor with anti-EBOV activity that limits EBOV pathogenesis.
埃博拉病毒(EBOV)是一种高致病性病毒,编码 7 种多功能结构蛋白。已经报道了多种宿主因子与 EBOV 蛋白相互作用。在这里,我们发现包含三部分基序的蛋白 14(TRIM14),一种干扰素刺激基因,介导与 I 型干扰素和炎症细胞因子产生相关的细胞信号通路,与 EBOV 核蛋白相互作用,增强干扰素-β(IFN-β)和核因子-κB(NF-κB)启动子的激活。此外,TRIM14 的过表达在传染性但生物隔离的 EBOVΔVP30 系统中使病毒复制减少了约 10 倍,而不影响病毒蛋白表达。此外,TRM14 缺陷型小鼠比野生型小鼠更容易感染经小鼠适应的 EBOV。我们的数据表明,TRIM14 是一种具有抗 EBOV 活性的宿主因子,可限制 EBOV 的发病机制。