Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.
PLoS Pathog. 2019 Nov 4;15(11):e1007634. doi: 10.1371/journal.ppat.1007634. eCollection 2019 Nov.
Induction of vast transcriptional programs is a central event of innate host responses to viral infections. Here we report a transcriptional program with potent antiviral activity, driven by E74-like ETS transcription factor 1 (ELF1). Using microscopy to quantify viral infection over time, we found that ELF1 inhibits eight diverse RNA and DNA viruses after multi-cycle replication. Elf1 deficiency results in enhanced susceptibility to influenza A virus infections in mice. ELF1 does not feed-forward to induce interferons, and ELF1's antiviral effect is not abolished by the absence of STAT1 or by inhibition of JAK phosphorylation. Accordingly, comparative expression analyses by RNA-seq revealed that the ELF1 transcriptional program is distinct from interferon signatures. Thus, ELF1 provides an additional layer of the innate host response, independent from the action of type I interferons.
诱导广泛的转录程序是先天宿主对病毒感染反应的中心事件。在这里，我们报告了一个具有强大抗病毒活性的转录程序，由 E74 样 ETS 转录因子 1（ELF1）驱动。我们使用显微镜来随时间量化病毒感染，发现 ELF1 在多轮复制后抑制八种不同的 RNA 和 DNA 病毒。Elf1 缺陷导致小鼠对甲型流感病毒感染的易感性增加。ELF1 不会正向诱导干扰素，并且 ELF1 的抗病毒作用不会因 STAT1 的缺失或 JAK 磷酸化的抑制而被消除。因此，通过 RNA-seq 进行的比较表达分析表明，ELF1 转录程序与干扰素特征不同。因此，ELF1 提供了先天宿主反应的额外层次，独立于 I 型干扰素的作用。
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