Poultry Science (Apr 2024)

IFI16 plays a critical role in avian reovirus induced cellular immunosuppression and suppresses virus replication

  • Zhang Chengcheng,
  • Zhang Qingqing,
  • Hu Xiaomiao,
  • Li Wei,
  • Zhang Xiaorong,
  • Wu Yantao

Journal volume & issue
Vol. 103, no. 4
p. 103506

Abstract

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ABSTRACT: Avian reovirus (ARV), which commonly induces viral arthritis or tenosynovitis and immunosuppression in chickens, is associated with the nonstructural protein p17 that plays a crucial role in viral replication and regulates cellular signaling pathways through its interaction with cellular proteins. In our previous study, we identified the host protein IFN-γ-inducible protein-16 (IFI16) as an interacting partner of ARV p17 through yeast two-hybrid screening. In the current study, we further confirmed the interaction between IFI16 and p17 protein using coimmunoprecipitation, glutathione S-transferase (GST)-pulldown assay, and laser confocal microscopy techniques. Additionally, we found that the amino acid of p1761-119 is responsible for mediating the interaction with the HINa and HINb domains of IFI16. Interestingly, we observed a significant increase in IFI16 expression upon ARV infection or p17 protein exposure. Moreover, the replication of ARV was found to be largely influenced by the quantity of IFI16 protein. Overexpression of IFI16 led to a significant decrease in ARV replication, while knockdown of the IFI16 expression led to the contrary result. Additionally, our findings demonstrate that IFI16 plays a crucial role in the induction of inflammatory cytokines IFN-β and IL-1β during ARV infection as confirmed by qRT-PCR and ELISA analyses. In conclusion, our study provides novel insights into the functional role of p17 protein and the pathogenic mechanism underlying ARV infection, particularly its association with inflammatory response. Furthermore, it offers new perspectives for identifying potential therapeutic targets against ARV infection.

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