RGD Reference Report - Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis.

Authors: Zhang, Ting  Yin, Chaoran  Boyd, David F  Quarato, Giovanni  Ingram, Justin P  Shubina, Maria  Ragan, Katherine B  Ishizuka, Takumi  Crawford, Jeremy Chase  Tummers, Bart  Rodriguez, Diego A  Xue, Jia  Peri, Suraj  Kaiser, William J  López, Carolina B  Xu, Yan  Upton, Jason W  Thomas, Paul G  Green, Douglas R  Balachandran, Siddharth 
Citation: Zhang T, etal., Cell. 2020 Mar 19;180(6):1115-1129.e13. doi: 10.1016/j.cell.2020.02.050.
RGD ID: 127229922
Pubmed: PMID:32200799   (View Abstract at PubMed)
PMCID: PMC7153753   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cell.2020.02.050   (Journal Full-text)

Influenza A virus (IAV) is a lytic RNA virus that triggers receptor-interacting serine/threonine-protein kinase 3 (RIPK3)-mediated pathways of apoptosis and mixed lineage kinase domain-like pseudokinase (MLKL)-dependent necroptosis in infected cells. ZBP1 initiates RIPK3-driven cell death by sensing IAV RNA and activating RIPK3. Here, we show that replicating IAV generates Z-RNAs, which activate ZBP1 in the nucleus of infected cells. ZBP1 then initiates RIPK3-mediated MLKL activation in the nucleus, resulting in nuclear envelope disruption, leakage of DNA into the cytosol, and eventual necroptosis. Cell death induced by nuclear MLKL was a potent activator of neutrophils, a cell type known to drive inflammatory pathology in virulent IAV disease. Consequently, MLKL-deficient mice manifest reduced nuclear disruption of lung epithelia, decreased neutrophil recruitment into infected lungs, and increased survival following a lethal dose of IAV. These results implicate Z-RNA as a new pathogen-associated molecular pattern and describe a ZBP1-initiated nucleus-to-plasma membrane "inside-out" death pathway with potentially pathogenic consequences in severe cases of influenza.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
influenza A exacerbatesISORipk3 (Mus musculus)127229922; 127229922 RGD 
influenza A exacerbatesIMP 127229922 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ripk3  (receptor-interacting serine-threonine kinase 3)

Genes (Mus musculus)
Ripk3  (receptor-interacting serine-threonine kinase 3)

Genes (Homo sapiens)
RIPK3  (receptor interacting serine/threonine kinase 3)


Additional Information