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

Authors: WEST, HALIE - Texas A&M University, Kingsville; Kaplan, Bryan; MAST, NATASHA - Texas A&M University, Kingsville; Sacco, Randy

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/31/2025
Publication Date: 1/3/2026
Citation: West, H.E., Kaplan, B.S., Mast, N.L., Sacco, R.E. 2025. Increased expression of the purinergic receptor P2Y6 in the bovine lung following experimental BRSV infection. Veterinary Immunology and Immunopathology. 292. Article 111060. https://doi.org/10.1016/j.vetimm.2025.111060.
DOI: https://doi.org/10.1016/j.vetimm.2025.111060

Interpretive Summary: Bovine respiratory syncytial virus (bRSV) is a cause of pneumonia in young calves. Furthermore, bRSV plays a role shipping fever, the most prevalent cause of morbidity and mortality among feedlot cattle. Economic costs to the American cattle industry from bovine respiratory diseases have been estimated to approach $1 billion annually due to death losses, reduced performance, and costs of vaccinations and treatment modalities. Recently, a molecule on the cell surface that senses danger signals to the host has been identified in viral infections. We provide the first evidence that this cell surface molecule increased in the lung during bRSV infections. Further studies are needed to determine if this increase plays a role in recruiting inflammatory cells to the lung that cause damage to the host.

Technical Abstract: Bovine respiratory disease (BRD), a polymicrobial disease complex, is a significant contributor to mortality in U.S. cattle herds. Bovine respiratory syncytial virus (BRSV) is a major viral pathogen frequently associated with BRD. Recent studies have identified P2Y6, a purinergic receptor to be involved in the recruitment of monocytes/macrophages and neutrophils as part of the host response to viral infections. P2Y6 is a G-protein-coupled purinergic receptor expressed by monocytes/macrophages, lymphocytes, and epithelial cells that recognizes uridine diphosphate, a danger-associated molecular pattern. P2Y6 signaling upregulates CCL-2, CXCL8, CXCL9, and CXCL10 expression. CXCL8, CXCL9, and CXCL10 are key pro-inflammatory chemokines previously shown to be upregulated during BRSV infection. Adenosine receptors are G-coupled purinergic receptors expressed on immune cell subsets whereby they participate in regulation of immune responses and inflammation. To examine the expression of purinergic receptors and proinflammatory chemokines during BRSV infection, Holstein calves were challenged with BRSV and euthanized on days 7 and 14 post-infection (DPI) to collect lung tissue samples 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. On day 7, P2Y6, CXCL9, and CXCL10 were significantly upregulated, while CCL2 and CXCL8 gene expression was also increased. In contrast, adenosine A3 receptor gene expression was lower than controls. At day 14, P2Y6 expression continued to be elevated compared to controls, while expression of chemokines was decreased. Future studies are needed to examine the potential role of P2Y6 in regulating chemokine induction during BRSV infection.