Shared host genetic landscape of respiratory viral infection
- Leah B. Soriaga
- Dale R. Balce
- Istvan Bartha
- Arnold Park
- Emily Wong
- Michael McAllaster
- Elizabeth A. Mueller
- Ona Barauskas
- Esteban Carabajal
- Beatriz Kowalski
- Sooyoung Lee
- Gary Lo
- Tara F. Mahoney
- Matteo Metruccio
- Anna Sahakyan
- Logeshwaran Somasundaram
- Tod Steinfeld
- Lisha Wang
- Laura Wedel
- Samantha S. Yim
- Li Yin
- Jiayi Zhou
- Zach Newby
- Winston Tse
- Johannes Grosse
- Herbert W. Virgin
- Seungmin Hwang
- Amalio Telenti
2025-05-15
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.