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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chen, Yung-chia Tseng, Chung-hsin Lai, Michael M. C. Su, Wen-chi Jeng, King-song Hsu, Paul Wei-che Tung, Kuo-feng |
| Description | Author Affiliation: Su WC ( Institute of Molecular Biology and National RNAi Core Facility, Academia Sinica, Taipei 11529, Taiwan.); |
| Abstract | Influenza viruses, like other viruses, rely on host factors to support their life cycle as viral proteins usually 'hijack,' or collaborate with, cellular proteins to execute their functions. Identification and understanding of these factors can increase the knowledge of molecular mechanisms manipulated by the viruses and facilitate development of antiviral drugs. To this end, we developed a unique genome-wide pooled shRNA screen to search for cellular factors important for influenza A virus (IAV) replication. We identified an E3 ubiquitin ligase, Itch, as an essential factor for an early step in the viral life cycle. In Itch knockdown cells, the incorporation of viral ribonucleoprotein complex into endosomes was normal, but its subsequent release from endosomes and transport to the nucleus was retarded. In addition, upon virus infection, Itch was phosphorylated and recruited to the endosomes, where virus particles were located. Furthermore, Itch interacted with viral M1 protein and ubiquitinated M1 protein. Collectively, our findings unravel a critical role of Itch in mediating IAV release from the endosome and offer insights into the mechanism for IAV uncoating during virus entry. These findings also highlight the feasibility of pooled RNAi screening for exploring the cellular cofactors of lytic viruses. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 43 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Endosomes Metabolism Influenza A Virus Growth & Development RNA Interference Repressor Proteins Ubiquitin-Protein Ligases Virus Internalization Animals Blotting, Western Cell Line Cell Line, Tumor Virology Genome, Human Genetics HEK293 Cells Host-Pathogen Interactions Physiology Microscopy, Fluorescence Phosphorylation Protein Binding Ubiquitination Viral Matrix Proteins Virus Replication Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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