ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death
| Autor: | Sannula Kesavardhana, Ashutosh Mishra, Thirumala-Devi Kanneganti, Teneema Kuriakose, Clifford S. Guy, Parimal Samir, R. K. Subbarao Malireddi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
ZBP1 Programmed cell death viruses Immunology Nerve Tissue Proteins Receptors Cell Surface RNA-binding protein Context (language use) Biology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Orthomyxoviridae Infections Influenza A virus medicine Animals Immunology and Allergy Research Articles Glycoproteins Ribonucleoprotein Mice Knockout Mice Inbred BALB C Cell Death Brief Definitive Report Ubiquitination virus diseases Membrane Proteins RNA-Binding Proteins Virology 3. Good health 030104 developmental biology Ribonucleoproteins Apoptosis Signal transduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20170550 |
| Popis: | The activation mechanism of ZBP1/DAI to regulate virus-induced programmed cell death is not known. Kesavardhana et al. show that ZBP1 senses viral ribonucleoproteins to induce cell death upon influenza A virus infection. Apical activation of RIG-I–IFNAR signaling to upregulate ZBP1 and influenza-induced ZBP1 ubiquitination are critical events for ZBP1 activation. Innate sensing of influenza virus infection induces activation of programmed cell death pathways. We have recently identified Z-DNA–binding protein 1 (ZBP1) as an innate sensor of influenza A virus (IAV). ZBP1-mediated IAV sensing is critical for triggering programmed cell death in the infected lungs. Surprisingly, little is known about the mechanisms regulating ZBP1 activation to induce programmed cell death. Here, we report that the sensing of IAV RNA by retinoic acid inducible gene I (RIG-I) initiates ZBP1-mediated cell death via the RIG-I–MAVS–IFN-β signaling axis. IAV infection induces ubiquitination of ZBP1, suggesting potential regulation of ZBP1 function through posttranslational modifications. We further demonstrate that ZBP1 senses viral ribonucleoprotein (vRNP) complexes of IAV to trigger cell death. These findings collectively indicate that ZBP1 activation requires RIG-I signaling, ubiquitination, and vRNP sensing to trigger activation of programmed cell death pathways during IAV infection. The mechanism of ZBP1 activation described here may have broader implications in the context of virus-induced cell death. |
| Databáze: | OpenAIRE |
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