系统地发现人类病原体和途径中的病原体效应功能，这一成果由多伦多大学Mikko Taipale课题组经过不懈努力而取得。这一研究成果发表在2026年6月30日出版的国际学术期刊《细胞》上。

小组开发了效应ORFeome (eORFeome)，这是一个可扩展的功能基因组学平台，包含来自不同病毒主题，细菌和寄生虫的3,835个效应子ORF。核因子κB （NF-κB）、凋亡、p53、cGAS-STING和主要组织相容性复合体I类（MHC I类）通路的高通量条形码筛选揭示了数百种未表征的eORFs的新通路调节功能、已知效应物的意外活性以及单个ORF编码的独特通路特异性功能。

为了证明这种方法的力量，该研究团队发现HHV6A U14是p53拮抗剂，HHV7 U21是双重功能的STING拮抗剂和MHC-I抗原显示抑制剂，腺病毒13.6K/i-先导蛋白是新进化的TAP抑制剂，抑制MHC-I显示。这些结果建立了系统效应物注释的一般框架，揭示了宿主-病原体相互作用的新机制，并突出了病原体效应物作为重新布线和探测人类细胞通路的多功能工具包。

研究人员表示，病原体利用效应蛋白来利用宿主细胞生物学，而大多数效应开放阅读框（ORFs）是快速进化的，缺乏功能注释。

附：英文原文

Title: Systematic discovery of pathogen effector functions across human pathogens and pathways

Author: Tomas Pachano, He Leng, Guillaume Dugied, Travis Tribble, Vincent Loubiere, Yeojin Lee, Felix Rauh, Victor Manon, Kevin Yuan, Jocelyn Nurtanto, Alexander Schleiffer, Veronika Young, Benjamin Weller, Eleanor A. Lyons, Matthew R. Hass, Leah C. Kottyan, Matthew T. Weirauch, Juan I. Fuxman Bass, Hayley J. Newton, Alexander W. Ensminger, Pascal Falter-Braun, Jue Chen, Daniel Schramek, Alexander Stark, Mikko Taipale

Issue&Volume: 2026-06-30

Abstract: Pathogens deploy effector proteins to exploit host cell biology, and most effector open reading frames (ORFs) are rapidly evolving and lack functional annotation. We developed the effector ORFeome (eORFeome), a scalable functional genomics platform encompassing 3,835 effector ORFs from diverse viruses, bacteria, and parasites. High-throughput barcoded screens across nuclear factor κB (NF-κB), apoptosis, p53, cGAS-STING, and major histocompatibility complex class I (MHC class I) pathways revealed novel pathway-modulating functions for hundreds of uncharacterized eORFs, unexpected activities of known effectors, and distinct pathway-specific functions encoded by single ORFs. Illustrating the power of this approach, we identified HHV6A U14 as a p53 antagonist, HHV7 U21 as a dual-function STING antagonist and MHC-I antigen display inhibitor, and adenoviral 13.6K/i-leader protein as a de novo-evolved TAP inhibitor that suppresses MHC-I display. These results establish a general framework for systematic effector annotation, uncover new mechanisms of host-pathogen interaction across kingdoms, and highlight pathogen effectors as a versatile toolkit for rewiring and probing human cellular pathways.

DOI: 10.1016/j.cell.2026.06.017

Source: https://www.cell.com/cell/abstract/S0092-8674(26)00704-X

期刊信息

Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：66.85

官方网址：https://www.cell.com/

投稿链接：https://www.editorialmanager.com/cell/default.aspx