效应触发免疫（ETI）是病原体感知的一种形式，涉及检测病原体编码的毒力因子或“效应物”。为了发现哺乳动物的ETI通路，小组开发了一种筛选方法，在人类单核细胞系中表达个体毒力因子，并通过RNA测序评估转录反应。该课题组研究人员发现了一种痘病毒效应物，黏液瘤病毒M3.1，它引发了抗病毒核因子κB （NF-κB）反应。NF-κB通过ETI通路释放，感知锌指抗病毒蛋白和TBK1两种抗病毒复合物的M3.1攻击。NF-κΒ的激活是由于M3.1-N4BP1、ZC3H12A和tbk1抑制的蛋白是NF-κB的负调节因子。他们的研究为发现ETI通路建立了一种系统的方法，结果阐明了免疫反应的负调节因子如何在病原体感知中起作用。
附：英文原文
Title: Poxvirus attack of antiviral defense pathways unleashes an effector-triggered NF-κB response
Author: Brenna C. Remick, Joshua Q. Mao, Andrew G. Manford, Ami D. Gutierrez-Jensen, Allon Wagner, Michael Rape, Grant McFadden, Masmudur M. Rahman, Moritz M. Gaidt, Russell E. Vance
Issue&Volume: 2026-02-12
Abstract: Effector-triggered immunity (ETI) is a form of pathogen sensing that involves detection of pathogen-encoded virulence factors or “effectors.” To discover ETI pathways in mammals, we developed a screening approach in which we expressed individual virulence factors in a human monocyte cell line and assessed transcriptional responses by RNA sequencing. We identified a poxvirus effector, myxoma virus M3.1, which elicited an antiviral nuclear factor κB (NF-κB) response. NF-κB was unleashed by an ETI pathway that sensed M3.1 attack of two antiviral complexes: zinc finger antiviral protein and TBK1. NF-κΒ activation occurred because the proteins inhibited by M3.1—N4BP1, ZC3H12A, and TBK1—are negative regulators of NF-κB. Our study established a systematic approach for the discovery of ETI pathways, and the results illustrated how negative regulators of immune responses may function in pathogen sensing.
DOI: adw4937
Source: https://www.science.org/doi/10.1126/science.adw4937