Increased expression of the purinergic receptor P2Y6 in the bovine lung following experimental BRSV infection

Abstract

Bovine respiratory syncytial virus (BRSV) is a major viral pathogen frequently associated with bovine respiratory disease complex. Recent studies identified P2Y6, a purinergic receptor to be involved in the recruitment of leukocytes as part of the host response to viral infections. P2Y6 is a G-protein-coupled purinergic receptor expressed by leukocytes and epithelial cells that recognizes uridine diphosphate, a danger-associated molecular pattern. P2Y6 signaling upregulates CCL-2, CXCL8, CXCL9, and CXCL10 expression. CXC chemokines were previously shown to be upregulated during BRSV infection. Adenosine receptors, G-protein-coupled purinergic receptors expressed on immune cell subsets, have immunoregulatory functions. To examine the expression of purinergic receptors and chemokines during BRSV infection, challenged Holstein calves were euthanized on 7 and 14 days post-infection (DPI) at peak and convalescing stages of infection, respectively. Real-time PCR and RNA in-situ hybridization were utilized to evaluate the expression of purinergic receptors and chemokines in lung samples. On 7 DPI, P2Y6, CXCL9, and CXCL10 were significantly upregulated. In contrast, adenosine A₃ receptor gene expression was lower than controls. On 14 DPI, P2Y6 expression trended higher compared to controls, while chemokine expression was decreased. Future studies are needed to examine the potential role of P2Y6 in regulating chemokine induction during BRSV infection.