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0Researchers have developed the eORFeome, a comprehensive functional genomics platform featuring nearly 4,000 effector open reading frames from diverse viruses, bacteria, and parasites. By conducting high-throughput barcoded lentiviral screens across five essential human signaling pathways, the authors identified hundreds of novel pathogen functions that manipulate host immunity and cell survival. Key discoveries include the HHV6A U14 protein acting as a potent p53 antagonist that promotes tumor growth and the HHV7 U21 protein serving as a dual inhibitor of both MHC-I display and STING signaling. Additionally, the study characterized the adenoviral 13.6K protein as a newly evolved inhibitor of the TAP transporter, further suppressing the host's ability to present antigens. This systematic resource establishes a powerful framework for annotating uncharacterized proteins and uncovers unique mechanisms of host-pathogen interactions. These findings highlight how pathogens serve as specialized tools for rewiring human cellular processes and identifying potential therapeutic vulnerabilities.
References:
Pachano T, Leng H, Dugied G, et al. Systematic discovery of pathogen effector functions across human pathogens and pathways[J]. Cell, 2025.
