Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
J Gen Virol. 2018 Nov;99(11):1463-1477. doi: 10.1099/jgv.0.001149. Epub 2018 Sep 20.
The interferon-induced proteins with tetratricopeptide repeats (IFITs) are a family of antiviral proteins conserved throughout all vertebrates. IFIT1 binds tightly to non-self RNA, particularly capped transcripts lacking methylation on the first cap-proximal nucleotide, and inhibits their translation by out-competing the cellular translation initiation apparatus. This exerts immense selection pressure on cytoplasmic RNA viruses to maintain mechanisms that protect their messenger RNA from IFIT1 recognition. However, it is becoming increasingly clear that protein-protein interactions are necessary for optimal IFIT function. Recently, IFIT1, IFIT2 and IFIT3 have been shown to form a functional complex in which IFIT3 serves as a central scaffold to regulate and/or enhance the antiviral functions of the other two components. Moreover, IFITs interact with other cellular proteins to expand their contribution to regulation of the host antiviral response by modulating innate immune signalling and apoptosis. Here, we summarize recent advances in our understanding of the IFIT complex and review how this impacts on the greater role of IFIT proteins in the innate antiviral response.
干扰素诱导的具有四肽重复的蛋白质（IFITs）是一类在所有脊椎动物中保守的抗病毒蛋白家族。IFIT1 可紧密结合非自身 RNA，特别是缺乏第一个帽近端核苷酸甲基化的加帽转录本，并通过与细胞翻译起始装置竞争来抑制其翻译。这对细胞质 RNA 病毒施加了巨大的选择压力，以维持保护其信使 RNA 免受 IFIT1 识别的机制。然而，越来越清楚的是，蛋白质-蛋白质相互作用对于 IFIT 的最佳功能是必要的。最近，IFIT1、IFIT2 和 IFIT3 已被证明形成了一个功能复合物，其中 IFIT3 作为中央支架来调节和/或增强其他两个成分的抗病毒功能。此外，IFIT 与其他细胞蛋白相互作用，通过调节先天免疫信号和细胞凋亡来扩大其对宿主抗病毒反应的调控作用。在这里，我们总结了我们对 IFIT 复合物的理解的最新进展，并回顾了这对 IFIT 蛋白在先天抗病毒反应中的更大作用的影响。
