Regulation of the p38 mitogen-activated protein kinase and dual-specificity phosphatase 1 feedback loop modulates the induction of interleukin 6 and 8 in cells infected with coronavirus infectious bronchitis virus

Induction of pro-inflammatory response is a crucial cellular process that detects and controls the invading viruses at early stages of the infection. Along with other innate immunity, this nonspecific response would either clear the invading viruses or allow the adaptive immune system to establish an effective antiviral response at late stages of the infection. The objective of this study was to characterize cellular mechanisms exploited by coronavirus infectious bronchitis virus (IBV) to regulate the induction of two pro-inflammatory cytokines, interleukin (IL)-6 and IL-8, at the transcriptional level. The results showed that IBV infection of cultured human and animal cells activated the p38 mitogen-activated protein kinase (MAPK) pathway and induced the expression of IL-6 and IL-8. Meanwhile, IBV has developed a strategy to counteract the induction of IL-6 and IL-8 by inducing the expression of dual-specificity phosphatase 1 (DUSP1), a negative regulator of the p38 MAPK, in order to limit the production of an excessive amount of IL-6 and IL-8 in the infected cells. As activation of the p38 MAPK pathway and induction of IL-6 and IL-8 may have multiple pathogenic effects on the whole host as well as on individual infected cells, regulation of the p38 MAPK and DUSP1 feedback loop by IBV may modulate the pathogenesis of the virus.