The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells
| العنوان: | The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells |
|---|---|
| المؤلفون: | Steve Goodbourn, Munir Iqbal, Wendy S. Barclay, Holly Shelton, Craig Ross, Joe James, Nikki Smith, Paul Digard |
| المصدر: | James, J, Smith, N, Ross, C, Iqbal, M, Goodbourn, S, Digard, P, Barclay, W S & Shelton, H 2019, ' The cellular localization of avian influenza virus PB1-F2 protein alters the magnitude of IFN2 promoter and NFκB-dependent promoter antagonism in chicken cells ', Journal of General Virology . https://doi.org/10.1099/jgv.0.001220Test |
| بيانات النشر: | Microbiology Society, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, animal structures, viruses, 030106 microbiology, Chicken Cells, Biology, medicine.disease_cause, Virus, Viral Proteins, 03 medical and health sciences, Virology, Influenza A Virus, H9N2 Subtype, Influenza A virus, medicine, Animals, Promoter Regions, Genetic, Gene, Poultry Diseases, Cellular localization, Influenza A Virus, H5N1 Subtype, NF-kappa B, virus diseases, Interferon-beta, biochemical phenomena, metabolism, and nutrition, In vitro, Cell biology, 030104 developmental biology, Cytoplasm, Influenza in Birds, Antagonism, Chickens |
| الوصف: | The accessory protein, PB1-F2, of influenza A virus (IAV) functions in a chicken host to prolong infectious virus shedding and thus the transmission window. Here we show that this delay in virus clearance by PB1-F2 in chickens is accompanied by reduced transcript levels of type 1 interferon (IFN)-induced genes and NFκB-activated pro-inflammation cytokines. In vitro, two avian influenza isolate-derived PB1-F2 proteins, H9N2 UDL01 and H5N1 5092, exhibited the same antagonism of the IFN and pro-inflammation induction pathways seen in vivo, but to different extents. The two PB1-F2 proteins had different cellular localization in chicken cells, with H5N1 5092 being predominantly mitochondrial-associated and H9N2 UDL being cytoplasmic but not mitochondrial-localized. We hypothesized that PB1-F2 localization might influence the functionality of the protein during infection and that the protein sequence could alter cellular localization. We demonstrated that the sequence of the C-terminus of PB1-F2 determined cytoplasmic localization in chicken cells and this was linked with protein instability. Mitochondrial localization of PB1-F2 resulted in reduced antagonism of an NFκB-dependent promoter. In parallel, mitochondrial localization of PB1-F2 increased the potency of chicken IFN 2 induction antagonism. We suggest that mitochondrial localization of PB1-F2 restricts interaction with cytoplasmic-located IKKβ, reducing NFκB-responsive promoter antagonism, but enhances antagonism of the IFN2 promoter through interaction with the mitochondrial adaptor MAVS. Our study highlights the differential mechanisms by which IAV PB1-F2 protein can dampen the avian host innate signalling response. |
| وصف الملف: | application/pdf |
| تدمد: | 1465-2099 0022-1317 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de9042f2c81408feccaebb57f5e61d68Test https://doi.org/10.1099/jgv.0.001220Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....de9042f2c81408feccaebb57f5e61d68 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14652099 00221317 |
|---|