Porcine adenovirus type 3 E1Blarge protein downregulates the induction of IL-8

Yan Zhou,Andrew Ficzycz,Suresh Kumar Tikoo

doi:10.1186/1743-422x-4-60

Abstract

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-κB 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-κB and its subsequent binding to DNA. These results suggest that E1Blarge interacts with NF-κB to prevent transcription and down regulate proinflammatory cytokine IL-8 production.

Highlights

Cytokines are important mediators of inflammation and regulators of the immune response
IL-8 transcript was the dominant chemokine gene induced in the cells infected with recombinant porcine adenovirus (PAdV)-3 containing deletion of E1A + E1Bsmall + E1Blarge + E3 (PAV227)
These results suggest that E1Blarge protein inhibit the expression of inflammatory cytokine IL-8

Summary

Introduction

Cytokines are important mediators of inflammation and regulators of the immune response. The inflammatory response including release of inflammatory cytokines is the first defense against viral infection. Adenovirus vector infection of airway epithelial A549 cells [12,13] or airways of macaques [14] results in rapid induction of the inflammatory cytokine IL-8, which may contribute to the inflammatory host response [12]. This induction of IL-8 production has been shown to be due to adenovirus induced activation of Raf/MAPK pathway [15]. Blocking these pathways may be required for developing an efficient adenovirus vector

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Conclusion