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0The paper details the creation of the eORFeome, a comprehensive functional genomics library containing nearly 4,000 pathogen effector proteins from various viruses, bacteria, and parasites. By utilizing high-throughput lentiviral screens, researchers systematically mapped how these effectors manipulate core human cellular processes, including immune signaling, apoptosis, and DNA damage responses. This large-scale effort successfully identified hundreds of novel functions, such as the HHV6A U14 protein acting as a potent p53 antagonist and the HHV7 U21 protein serving as a dual inhibitor of both STING and MHC-I pathways. Furthermore, the study uncovered a de novo-evolved adenoviral protein that suppresses immune detection by inhibiting the TAP transporter. Ultimately, this work establishes a robust framework for pathogen protein annotation and highlights how evolutionarily optimized effectors can be used as tools to probe and rewire human cell biology.
References:
Pachano T, Leng H, Dugied G, et al. Systematic discovery of pathogen effector functions across human pathogens and pathways[J]. Cell, 2025.
