Unknown

Dataset Information

0

ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death.


ABSTRACT: 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.

SUBMITTER: Kesavardhana S 

PROVIDER: S-EPMC5551577 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

altmetric image

Publications

ZBP1/DAI ubiquitination and sensing of influenza vRNPs activate programmed cell death.

Kesavardhana Sannula S   Kuriakose Teneema T   Guy Clifford S CS   Samir Parimal P   Malireddi R K Subbarao RKS   Mishra Ashutosh A   Kanneganti Thirumala-Devi TD  

The Journal of experimental medicine 20170620 8


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)  ...[more]

Similar Datasets

| S-EPMC5131924 | biostudies-literature
| S-EPMC5687825 | biostudies-literature
2016-09-27 | GSE87372 | GEO
| S-EPMC6744433 | biostudies-literature
| S-EPMC2238155 | biostudies-literature
| S-EPMC10070280 | biostudies-literature
| S-EPMC4480161 | biostudies-literature
| S-EPMC4014071 | biostudies-literature
| S-EPMC9222173 | biostudies-literature
| S-EPMC6251052 | biostudies-literature