Wnt14 regulates the cellular inflammation induced by avian reovirus and interacts with the viral σB protein.

Abstract

Avian reovirus (ARV) typically induces viral arthritis or tenosynovitis in chickens. The ARV structural protein σB plays a crucial role in viral replication and regulates cellular signaling pathways through interactions with host proteins. In this study, we demonstrate that both ARV infection and ARV σB protein can activate intracellular Wnt signaling pathways and induce inflammatory responses based on qPCR and Western blot analyses in HD11 cells. Interestingly, ARV infection can inhibit β-catenin ubiquitination and upregulate its protein expression levels. To further investigate the mechanism of this phenomenon, the quantity of ARV replication and the expression of inflammation cytokine IL-1β were both significantly increased when overexpression of Wnt14 protein. Conversely, shRNA-mediated knockdown of endogenous Wnt14 expression substantially suppressed ARV replication and virus-induced inflammatory responses. Furthermore, the inflammatory response was concomitantly attenuated in parallel with the suppression of ARV replication in the condition of pretreated with Wnt inhibitor. Finally, the direct interaction of ARV σB and Wnt14 protein was confirmed by using immunoprecipitation, glutathione S-transferase (GST)-pulldown assay. We further observed the colocalization of σB and Wnt14 protein by laser scanning microscopy techniques. The cellular Wnt signaling pathway regulated by ARV may mediated through this direct interaction between σB protein and Wnt14. In summary, our research provides new insights into the functional role of σB protein as well as elucidating pathogenic mechanisms associated with ARV infection-particularly its relationship with inflammatory responses.