دورية أكاديمية
Integrated multi-omics analyses identify anti-viral host factors and pathways controlling SARS-CoV-2 infection
| العنوان: | Integrated multi-omics analyses identify anti-viral host factors and pathways controlling SARS-CoV-2 infection |
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| المؤلفون: | Hou, Jiakai, Wei, Yanjun, Zou, Jing, Jaffery, Roshni, Sun, Long, Liang, Shaoheng, Zheng, Ningbo, Guerrero, Ashley M., Egan, Nicholas A., Bohat, Ritu, Chen, Si, Zheng, Caishang, Mao, Xiaobo, Yi, S. Stephen, Chen, Ken, McGrail, Daniel J., Sahni, Nidhi, Shi, Pei-Yong, Chen, Yiwen, Xie, Xuping, Peng, Weiyi |
| المساهمون: | University of Houston, Cancer Prevention and Research Institute of Texas |
| المصدر: | Nature Communications ; volume 15, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-Seq, and host-virus proteins or protein/RNA interactome. This study uncovers many host factors that are currently underappreciated, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that modulate viral entry and/or replication. The cohesin complex is also identified as an anti-viral pathway, suggesting an important role of three-dimensional chromatin organization in mediating host-viral interaction. Furthermore, we discover another anti-viral regulator KLF5, a transcriptional factor involved in sphingolipid metabolism, which is up-regulated, and harbors genetic variations linked to COVID-19 patients with severe symptoms. Anti-viral effects of three identified candidates (DAZAP2/VTA1/KLF5) are confirmed individually. Molecular characterization of DAZAP2/VTA1/KLF5-knockout cells highlights the involvement of genes related to the coagulation system in determining the severity of COVID-19. Together, our results provide further resources for understanding the host anti-viral network during SARS-CoV-2 infection and may help develop new countermeasure strategies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-44175-1 |
| الإتاحة: | https://doi.org/10.1038/s41467-023-44175-1Test https://www.nature.com/articles/s41467-023-44175-1.pdfTest https://www.nature.com/articles/s41467-023-44175-1Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.3029E7A0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-44175-1 |
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