Suppression of the antiviral response by an influenza histone mimic

摘要

组蛋白是基因功能的必要调控因子。NH2-端部或组蛋白“尾”可以被“翻译后修饰”，对控制基因功能的蛋白复合物的组装来说起个脚手架的作用。现在，Ivan Marazzi及其同事发现，流感病毒的免疫抑制性NSl蛋白携带一个与组蛋白相似的序列，模仿组蛋白H3的关键特征，其中包括与关键转录调控因子的结合，所以该病毒能够劫持宿主的转录机器。%Viral infection is commonly associated with virus-driven hijacking of host proteins. Here we describe a novel mechanism by which influenza virus affects host cells through the interaction of influenza non-structural protein 1 (NS1) with the infected cell epigenome. We show that the NS1 protein of influenza A H3N2 subtype possesses a histone-like sequence (histone mimic) that is used by the virus to target the human PAF1 transcription elongation complex (hPAF1C). We demonstrate that binding of NS1 to hPAF1C depends on the NS1 histone mimic and results in suppression of hPAF1C-mediated transcriptional elongation. Furthermore, human PAF1 has a crucial role in the antiviral response. Loss of hPAF1C binding by NS1 attenuates influenza infection, whereas hPAF1C deficiency reduces antiviral gene expression and renders cells more susceptible to viruses. We propose that the histone mimic in NS1 enables the influenza virus to affect inducible gene expression selectively, thus contributing to suppression of the antiviral response.