Restriction factor compendium for influenza A virus reveals a mechanism for evasion of autophagy
| Autor: | Courtney Nguyen, Danielle L. Swaney, Lars Pache, Hong M. Moulton, David A. Stein, Shashank Tripathi, Dexter Pratt, Trey Ideker, Stephen Soonthornvacharin, David Jimenez-Morales, Maite Sanchez-Aparicio, Nish Beltran-Raygoza, Paul D. De Jesus, Randy A. Albrecht, Kelsey M. Haas, Adolfo García-Sastre, Judd F. Hultquist, João I. Mamede, Guojun Wang, Laura Martin-Sancho, Ariel Rodriguez-Frandsen, Christopher Churas, Max W. Chang, Sara Brin Rosenthal, Thong T. Nguyen, Nevan J. Krogan, Sumit K. Chanda, Michael J. McGregor, Laura Riva, Christopher Benner |
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| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Immunology Regulator Biology Virus Replication medicine.disease_cause Proteomics Antiviral Agents Applied Microbiology and Biotechnology Microbiology Article Viral Matrix Proteins Vaccine Related Cell membrane Transcriptome Biodefense Autophagy Genetics Influenza A virus medicine Humans 2.2 Factors relating to the physical environment 2.1 Biological and endogenous factors Aetiology Immune Evasion Prevention GTPase-Activating Proteins rab7 GTP-Binding Proteins Cell Biology Influenza In vitro Cell biology Infectious Diseases Emerging Infectious Diseases medicine.anatomical_structure rab GTP-Binding Proteins Medical Microbiology Cytoplasm Host-Pathogen Interactions Pneumonia & Influenza Lysosomes Infection Protein Binding |
| Zdroj: | Nature microbiology, vol 6, iss 10 Nat Microbiol |
| ISSN: | 2058-5276 |
| Popis: | The fate of influenza A virus (IAV) infection in the host cell depends on the balance between cellular defence mechanisms and viral evasion strategies. To illuminate the landscape of IAV cellular restriction, we generated and integrated global genetic loss-of-function screens with transcriptomics and proteomics data. Our multi-omics analysis revealed a subset of both IFN-dependent and independent cellular defence mechanisms that inhibit IAV replication. Amongst these, the autophagy regulator TBC1 domain family member 5 (TBC1D5), which binds Rab7 to enable fusion of autophagosomes and lysosomes, was found to control IAV replication in vitro and in vivo and to promote lysosomal targeting of IAV M2 protein. Notably, IAV M2 was observed to abrogate TBC1D5-Rab7 binding through a physical interaction with TBC1D5 via its cytoplasmic tail. Our results provide evidence for the molecular mechanism utilised by IAV M2 protein to escape lysosomal degradation and traffic to the cell membrane, where it supports IAV budding and growth. |
| Databáze: | OpenAIRE |
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