Interferon-stimulated genes (ISGs) are a group of gene products that coordinately combat pathogen invasions, in particular viral infections. Transcription of ISGs occurs rapidly upon pathogen invasion, and this is classically provoked via activation of the Janus kinase/signal transducer and activator of transcription (JAK–STAT) pathway, mainly by interferons (IFNs). However, a plethora of recent studies have reported a variety of non-canonical mechanisms regulating ISG transcription. These new studies are extremely important for understanding the quantitative and temporal differences in ISG transcription under specific circumstances. Because these canonical and non-canonical regulatory mechanisms are essential for defining the nature of host defense and associated detrimental proinflammatory effects, we comprehensively review the state of this rapidly evolving field and the clinical implications of recently acquired knowledge in this respect.

干扰素刺激基因（ISG）是一组基因产物，可以协调对抗病原体的入侵，特别是病毒感染。ISG的转录在病原体入侵后迅速发生，这通常是通过Janus激酶/信号转导子和转录激活子（JAK–STAT）途径（主要是干扰素）的激活引起的。但是，最近的大量研究报告了多种调节ISG转录的非经典机制。这些新研究对于理解特定情况下ISG转录的数量和时间差异极为重要。由于这些规范性和非规范性调节机制对于定义宿主防御的性质和相关的有害促炎作用至关重要，