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Updated: Jul 4, 2026

High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
Published on: March 5, 2022
A viral ORFeome library for systems-level genetic dissection of host-pathogen interactions
Eric Fujimura1, Colin N O'Leary2, Mamie Z Li3
1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Program in Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02115, USA.
None:
Virological research has traditionally focused on individual viruses or viral families. Advances in DNA synthesis now allow large-scale construction of individual gene products, enabling systematic exploration of the virome. Here, we developed a barcoded library of ∼12,000 viral open reading frames (vORFs) from 513 viral species, which we leveraged to identify hundreds of viral regulators of cellular proliferation, MHC class I antigen presentation, and interferon signaling. Integrating results across these screens revealed unique phenotypic profiles and functional vORF modules, allowing the in-depth characterization of two previously uncharacterized viral proteins, MC162R and Yaba-like disease virus (YLDV) 151R, which impair MHC class I antigen presentation and interferon (IFN)-β signaling, respectively. Together, the viral ORFeome provides a scalable framework for dissecting viral protein function across the breadth of the virome.
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