Shared host genetic landscape of respiratory viral infection

• 成果类型: Article
• 署名作者: Soriaga, Leah B.; Balce, Dale R.; Bartha, Istvan; Park, Arnold; Wong, Emily; McAllaster, Michael; Mueller, Elizabeth A.; Barauskas, Ona; Carabajal, Esteban; Kowalski, Beatriz; Lee, Sooyoung; Lo, Gary; Mahoney, Tara F.; Metruccio, Matteo; Sahakyan, Anna; Somasundaram, Logeshwaran; Steinfeld, Tod; Wang, Lisha; Wedel, Laura; Yim, Samantha S.; Yin, Li; Zhou, Jiayi; Newby, Zach; Tse, Winston; Grosse, Johannes; Virgin, Herbert W.; Hwang, Seungmin; Telenti, Amalio
• 署名单位: Washington University (WUSTL); University of Texas System; University of Texas Southwestern Medical Center; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12224
• DOI: 10.1073/pnas.2414202122
• 发表日期: 2025-05-20
• 关键词: influenza-virus; receptor; sars-cov-2; screen; target; entry

摘要

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.