Porcine adenovirus type 3 E1B large protein downregulates the induction of IL-8.
Replication-defective (E1-E3 deleted) adenovirus vector based gene delivery results in the induction of cytokines including IL-8, which may contribute to the development of inflammatory immune responses. Like other adenoviruses, E1 + E3 deleted porcine adenovirus (PAdV) 3 induces the production of IL-8 in infected cells. In contrast, no IL-8 production could be detected in cells infected with wild-type or mutant PAdV-3s containing deletion in E1A + E3 (PAV211) or E1Bsmall + E3 (PAV212). Expression of PAdV-3 E1Blarge inhibited the NF-kappaB dependent transcription of luciferase from IL-8 promoter. Imunofluorescence and electrophoretic mobility shift assays suggested that constitutive expression of PAdV-3 E1Blarge inhibited the nuclear translocation of NF-kappaB and its subsequent binding to DNA. These results suggest that E1Blarge interacts with NF-kappaB to prevent transcription and down regulate proinflammatory cytokine IL-8 production.
Zhou
Yan
Y
Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. yan.zhou@usask.ca
Ficzycz
Andrew
A
Tikoo
Suresh Kumar
SK
D021581:Active Transport, Cell Nucleus; D017501:Adenovirus E1B Proteins / Q000378:metabolism*; D025662:Adenoviruses, Porcine / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D019677:Artificial Gene Fusion; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D013552:Swine
D017501:Adenovirus E1B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D008156:Luciferases