Systematic discovery of pathogen effector functions across human pathogens and pathways.

Effector ORFeome screens uncovered 3,835 pathogen effector functions, revealing novel and pathway-specific activities across human cellular pathways.

• Why it matters: Understanding how pathogen effectors manipulate host biology is crucial for developing targeted therapies and comprehending host-pathogen interactions, especially given their rapid evolution and limited functional annotation.
• What they did: A scalable platform was created to analyze 3,835 effector ORFs from diverse pathogens using high-throughput barcoded screens across key human immune pathways, including NF-κB, apoptosis, p53, cGAS-STING, and MHC class I.
• The result: The study identified new effector functions, such as viral antagonists of p53 and STING, and a de novo TAP inhibitor, providing insights into pathogen strategies and offering a framework for systematic effector annotation and pathway probing.