دورية أكاديمية
Cellular glycan modification by B3GAT1 broadly restricts influenza virus infection
| العنوان: | Cellular glycan modification by B3GAT1 broadly restricts influenza virus infection |
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| المؤلفون: | Trimarco, Joseph D., Nelson, Sarah L., Chaparian, Ryan R., Wells, Alexandra I., Murray, Nathan B., Azadi, Parastoo, Coyne, Carolyn B., Heaton, Nicholas S. |
| المساهمون: | U.S. Department of Health & Human Services | NIH | National Cancer Institute, U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases, U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences, United States Department of Defense | Defense Advanced Research Projects Agency |
| المصدر: | Nature Communications ; volume 13, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Communicable respiratory viral infections pose both epidemic and pandemic threats and broad-spectrum antiviral strategies could improve preparedness for these events. To discover host antiviral restriction factors that may act as suitable targets for the development of host-directed antiviral therapies, we here conduct a whole-genome CRISPR activation screen with influenza B virus (IBV). A top hit from our screen, beta-1,3-glucuronyltransferase 1 (B3GAT1), effectively blocks IBV infection. Subsequent studies reveal that B3GAT1 activity prevents cell surface sialic acid expression. Due to this mechanism of action, B3GAT1 expression broadly restricts infection with viruses that require sialic acid for entry, including Victoria and Yamagata lineage IBVs, H1N1/H3N2 influenza A viruses (IAVs), and the unrelated enterovirus D68. To understand the potential utility of B3GAT1 induction as an antiviral strategy in vivo, we specifically express B3GAT1 in the murine respiratory epithelium and find that overexpression is not only well-tolerated, but also protects female mice from a lethal viral challenge with multiple influenza viruses, including a pandemic-like H1N1 IAV. Thus, B3GAT1 may represent a host-directed broad-spectrum antiviral target with utility against clinically relevant respiratory viruses. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-022-34111-0 |
| الإتاحة: | https://doi.org/10.1038/s41467-022-34111-0Test https://www.nature.com/articles/s41467-022-34111-0.pdfTest https://www.nature.com/articles/s41467-022-34111-0Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.B7900AFB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-022-34111-0 |
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