title: RIPK3 Is Largely Dispensable for RIG-I-Like Receptor- and Type I Interferon-Driven Transcriptional Responses to Influenza A Virus in Murine Fibroblasts.
abstract: The kinase RIPK3 is a key regulator of cell death responses to a growing number of viral and microbial agents. We have found that influenza A virus (IAV)-mediated cell death is largely reliant on RIPK3 and that RIPK3-deficient mice are notably more susceptible to lethal infection by IAV than their wild-type counterparts. Recent studies demonstrate that RIPK3 also participates in regulating gene transcription programs during host pro-inflammatory and innate-immune responses, indicating that this kinase is not solely an inducer of cell death and that RIPK3-driven transcriptional responses may collaborate with cell death in promoting clearance of IAV. Here, we carried out DNA microarray analyses to determine the contribution of RIPK3 to the IAV-elicited host transcriptional response. We report that RIPK3 does not contribute significantly to the RLR-activated transcriptome or to the induction of type I IFN genes, although, interestingly, IFN-β production at a post-transcriptional step was modestly attenuated in IAV-infected ripk3-/- fibroblasts. Overall, RIPK3 regulated the expression of <5% of the IAV-induced transcriptome, and no genes were found to be obligate RIPK3 targets. IFN-β signaling was also found to be largely normal in the absence of RIPK3. Together, these results indicate that RIPK3 is not essential for the host antiviral transcriptional response to IAV in murine fibroblasts.
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Shoko
authors.initials: S
authors.lastname: Nogusa
authors.affiliation: Department of Bioinformatics and Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Slifker
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Justin P
authors.initials: JP
authors.lastname: Ingram
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Roshan J
authors.initials: RJ
authors.lastname: Thapa
authors.affiliation: Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Balachandran
mesh_terms: D000818:Animals; D000071457:DEAD Box Protein 58 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology*; D009980:Influenza A virus / Q000378:metabolism* / Q000472:pathogenicity*; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
chemical_list: D007370:Interferon Type I; D016899:Interferon-beta; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C485615:Ripk3 protein, mouse; D000071457:DEAD Box Protein 58