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Updated: Jul 4, 2026
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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.
Cell
|July 2, 2026
Summary
Researchers created a library of 12,000 viral gene products to discover how viruses impact cell functions. This approach identified hundreds of viral regulators and characterized two new viral proteins affecting immune responses.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Traditional virological research often examines viruses individually.
- Recent advances in DNA synthesis enable large-scale creation of viral gene products.
- Systematic exploration of the virome is now feasible.
Purpose of the Study:
- To develop a comprehensive library of viral open reading frames (vORFs).
- To systematically screen vORFs for regulatory functions in host cellular processes.
- To characterize novel viral proteins impacting host immunity.
Main Methods:
- Construction of a barcoded library of approximately 12,000 vORFs from 513 viral species.
- High-throughput screening to identify viral regulators of cellular proliferation, MHC class I antigen presentation, and interferon signaling.
- Integration of screening data to reveal phenotypic profiles and functional vORF modules.
Main Results:
- Identification of hundreds of viral regulators affecting key cellular pathways.
- Characterization of two previously unstudied viral proteins: MC162R and Yaba-like disease virus (YLDV) 151R.
- MC162R was found to impair MHC class I antigen presentation, while YLDV 151R inhibits interferon (IFN)-β signaling.
Conclusions:
- The viral ORFeome serves as a scalable framework for functional virome exploration.
- This approach facilitates the in-depth characterization of viral protein functions across diverse viruses.
- Understanding viral regulators provides insights into host-pathogen interactions and viral pathogenesis.
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