Canine coronavirus activates the aryl hydrocarbon receptor during infection

Introduction - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that interacts with various endogenous and exogenous substrates such as bilirubin, biliverdin, tryptophan metabolites, environmental pollutants, as well as microbial metabolites. After the activation, AhR translocates into the nucleus where it controls the expression of target genes, including AhR repressor, detoxifying monooxygenases, and cytokines. Current findings establish that AhR signaling can influence intrinsic, innate and adaptive immune response to different microorganisms. Recently, it has been demonstrated a role for AhR as a controller of the host response to Coronaviruses (CoVs) (MCoV, SARS-CoV-2, HCoV 229E) infection. Genotype II of canine coronavirus (CCoV-II), an alphacoronavirus, can provoke moderate to severe enteric disease in dogs. Herein, we tested the involvment of AhR in CCoV infection. Materials and methods - Infection of CCoV (378/strain) in canine fibrosarcoma (A72) cell line was carried out in the presence of CH22319149, an AhR antagonist. Bioscreen, immunofluorescence, and virus yield analyses were performed. Results - During CCoV infection an upregulation of AhR was detected. The non-toxic concentration of 2 MCH22319149 markedly decreased cell death signs and increased cell viability. Furthermore, the AhR antagonist provoked a considerable decrease in virus yield. These results were accompanied by the inhibition of the expression of viral nuclear protein. Discussion and Conclusions - Overall, our findings demonstrate that infection with CCoV activates AhR. In addition, pharmacologic AhR inhibition provokes a reduction in CoVs replication in vitro, identifying AhR as a conceivable candidate target for antiviral therapy.