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

2017 ◽  
Vol 214 (8) ◽  
pp. 2217-2229 ◽  
Author(s):  
Sannula Kesavardhana ◽  
Teneema Kuriakose ◽  
Clifford S. Guy ◽  
Parimal Samir ◽  
R.K. Subbarao Malireddi ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Posttranslational Modifications ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Dna Binding Protein ◽  
Cell Death Pathways ◽  
Signaling Axis ◽  
Trigger Cell Death ◽  
Inducible Gene

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.

scholarly journals Innate Immune sensing of Influenza A viral RNA through IFI16 promotes pyroptotic cell death

2021 ◽  
Author(s):  
Shalabh Mishra ◽  
Athira S Raj ◽  
Akhilesh Kumar ◽  
Ashwathi Rajeevan ◽  
Puja Kumari ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Influenza A Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Type I ◽  
Cell Death Pathways ◽  
Infected Cells ◽  
Immune Sensing

AbstractProgrammed cell death pathways are triggered by various stresses or stimuli, including viral infections. The mechanism underlying the regulation of these pathways upon Influenza A virus IAV infection is not well characterized. We report that a cytosolic DNA sensor IFI16 is essential for the activation of programmed cell death pathways in IAV infected cells. We have identified that IFI16 functions as an RNA sensor for influenza A virus by binding to genomic RNA. The activation of IFI16 triggers the production of type I, III interferons, and also other pro-inflammatory cytokines via the STING-TBK1 and Pro-caspase-1 signaling axis, thereby promoting cell death (apoptosis and pyroptosis in IAV infected cells). Whereas, IFI16 knockdown cells showed reduced inflammatory responses and also prevented cell mortality during IAV infection. These results demonstrate the pivotal role of IFI16-mediated IAV sensing and its essential role in activating programmed cell death pathways.

scholarly journals Polymerase Acidic Subunit of H9N2 Polymerase Complex Induces Cell Apoptosis by Binding to PDCD 7 in A549 Cells

2020 ◽  
Author(s):  
Shaohua Wang ◽  
Na Li ◽  
Shugang Jin ◽  
Ruihua Zhang ◽  
Tong Xu
Keyword(s):  
Cell Death ◽  
Influenza Virus ◽  
Cell Apoptosis ◽  
Influenza A ◽  
A549 Cells ◽  
Influenza Virus Infection ◽  
Economic Loss ◽  
Poultry Production ◽  
H9n2 Influenza Virus

Abstract Background: H9N2 influenza virus, a subtype of influenza A virus, can spread across different species and induce the respiratory infectious disease in humans, leading to a severe public health risk and a huge economic loss to poultry production. Increasing studies have shown that polymerase acidic (PA) subunit of RNA polymerase in ribonucleoproteins complex of H9N2 involves in crossing the host species barriers, the replication and airborne transmission of H9N2.Methods: Here, to further investigate the role of PA subunit during the infection of H9N2 influenza virus, we employed mass spectrometry (MS) to search the potential binding proteins of PA subunit of H9N2. Our MS results showed that programmed cell death protein 7 (PDCD7) is a binding target of PA subunit. Co-immunoprecipitation and pull-down assays further confirmed the interaction between PDCD7 and PA subunit. Overexpression of PA subunit in A549 lung cells greatly increased the levels of PDCD7 in the nuclear and induced cell death assayed by MTT assay.Results: Flow cytometry analysis and Western blot results showed that PA subunit overexpression significantly increased the expression of pro-apoptotic protein, bax and caspase 3, and induced cell apoptosis. However, knockout of PDCD7 effectively attenuated the effects of PA overexpression in cell apoptosis.Conclusions: In conclusion, the PA subunit of H9N2 bind with PDCD7 and regulated cell apoptosis, which provide new insights in the role of PA subunit during H9N2 influenza virus infection.

Mitochondrial DNA–Related Mitochondrial Dysfunction in Neurodegenerative Diseases

2002 ◽  
Vol 126 (3) ◽  
pp. 271-280
Author(s):  
Russell H. Swerdlow
Keyword(s):  
Cell Death ◽  
Mitochondrial Dna ◽  
Programmed Cell Death ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Cell Lines ◽  
Late Onset ◽  
Cell Death Pathways ◽  
Mitochondrial Genotype ◽  
Cybrid Cell

Abstract Mitochondrial dysfunction occurs in several late-onset neurodegenerative diseases. Determining its origin and significance may provide insight into the pathogeneses of these disorders. Regarding origin, one hypothesis proposes mitochondrial dysfunction is driven by mitochondrial DNA (mtDNA) aberration. This hypothesis is primarily supported by data from studies of cytoplasmic hybrid (cybrid) cell lines, which facilitate the study of mitochondrial genotype-phenotype relationships. In cybrid cell lines in which mtDNA from persons with certain neurodegenerative diseases is assessed, mitochondrial physiology is altered in ways that are potentially relevant to programmed cell death pathways. Connecting mtDNA-related mitochondrial dysfunction with programmed cell death underscores the crucial if not central role for these organelles in neurodegenerative pathophysiology. This review discusses the cybrid technique and summarizes cybrid data implicating mtDNA-related mitochondrial dysfunction in certain neurodegenerative diseases.

MicroRNA Regulation of Programmed Cell Death Pathways in Cancer

2012 ◽  
Vol 6 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Miao Ming ◽  
Xu Zhao ◽  
Zi-yi Zhao ◽  
Bo Liu ◽  
Jin-ku Bao
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Microrna Regulation ◽  
Cell Death Pathways
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