Shared host genetic landscape of respiratory viral infection
Respiratory viruses represent a major global health burden. Although these viruses have different life cycles, they may depend on common host genetic factors, which could be targeted by broad-spectrum host-directed therapies. We used genome-wide CRISPR screens and advanced data analytics to map a network of host genes that support infection by nine human respiratory viruses [influenza A virus, parainfluenza virus, human rhinovirus, respiratory syncytial virus, human coronavirus (HCoV)-229E, HCoV-NL63, HCoV-OC43, Middle East respiratory syndrome-related coronavirus, and severe acute respiratory syndrome-related coronavirus 2]. We explored shared pathways using knowledge graphs to inform on pharmacological targets. We selected and validated STT3A/B proteins of the N-oligosaccharyltransferase complex as host targets of broad-spectrum antiviral small molecules. Our work highlights the commonalities of viral host genetic dependencies and the feasibility of using this information to develop broad-spectrum antiviral agents.
Authors
- Jiayi Zhou (ORCID: https://orcid.org/0000-0002-4231-3422)
- Anna Sahakyan (ORCID: https://orcid.org/0000-0002-8840-9171)
- Michael R. McAllaster (ORCID: https://orcid.org/0000-0001-9729-7290)
- Ona Barauskas (ORCID: https://orcid.org/0000-0001-9878-5763)
- Johannes Grosse (ORCID: https://orcid.org/0000-0003-3288-0455)
- Matteo M. E. Metruccio (ORCID: https://orcid.org/0000-0002-2456-2652)
- Elizabeth A. Mueller (ORCID: https://orcid.org/0000-0001-5482-6551)
- Herbert W. Virgin (ORCID: https://orcid.org/0000-0001-8580-7628)
- Dale R. Balce (ORCID: https://orcid.org/0000-0001-5123-530X)
- Laura Wedel
- Leah Soriaga (ORCID: https://orcid.org/0000-0001-5852-741X)
- Tod Steinfeld
- Amalio Telenti (ORCID: https://orcid.org/0000-0001-6290-7677)
- István Bartha (ORCID: https://orcid.org/0000-0003-3360-1999)
- Arnold Park (ORCID: https://orcid.org/0000-0001-8916-2230)
- Zachary E. Newby
- Seungmin Hwang (ORCID: https://orcid.org/0000-0003-0846-5462)
- Winston C. Tse
- Samantha S. Yim (ORCID: https://orcid.org/0009-0007-8567-3501)
- Soo-Young Lee (ORCID: https://orcid.org/0000-0002-3306-9333)
- Lisha Wang (ORCID: https://orcid.org/0000-0002-6482-1073)
- Li Yin (ORCID: https://orcid.org/0000-0003-2634-9158)
- B. Kowalski
- Timothy R. Mahoney
- Esteban Carabajal
- G.F. Lo
- Logeshwaran Somasundaram
- Emily Wong
Institutions
- VIR Biotechnology (United States) (US)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-05-15
- DOI
- https://doi.org/10.1073/pnas.2414202122
- Citations
- 2
- Primary Topic
- Respiratory viral infections research
- Type
- article
- Field-Weighted Citation Impact
- 2.71
Funders
- Massachusetts Institute of Technology
- Washington University in St. Louis
- Broad Institute
- Vir Biotechnology