Marek's disease virus (MDV) is an economic concern for the poultry industry due to its poorly understood pathophysiology. Purinergic receptors (PRs) are potential therapeutic targets for viral infections, including herpesviruses, prompting our investigation into their role in MDV pathogenesis. The current study is part of an experimental series analyzing the expression of PRs during MDV infection. To address the early or short-acting P2 PR responses during natural MDV infection, we performed an "exposure" experiment where age-matched chickens were exposed to experimentally infected shedders to initiate natural infection. In addition, select non-PR regulatory gene responses were measured. Two groups of naïve contact chickens (n = 5/breed/time point) from MD-resistant (White Leghorns: WL) and -susceptible (Pure Columbian) chicken lines were housed separately with experimentally infected PC (×PC) and WL (×WL) chickens for 6 or 24 h. Whole lung lavage cells (WLLC) were collected, RNA was extracted, and RT-qPCR assays were used to measure specific PR responses. In addition, other potentially important markers in pathophysiology were measured. Our study revealed that WL chickens exhibited higher P1 PR expression during natural infection. WL chickens also showed higher expression of and at 6 and 24 h when exposed to PC-infected chickens. and showed higher expression at 6 h, while P2Y5 showed higher expression at 6 and 24 h; regardless of the chicken line, PC chickens exhibited higher expression of , , , and when exposed to either group of infected chickens. In addition, MDV infection altered the expression of in both WL and PC groups exposed to PC-infected birds only. However, irrespective of the source of exposure, BCL2 and showed higher expression in both WL and PC. The expression of and was influenced by time and breed, with major changes observed in . and expression significantly increased in both WL and PC birds, regardless of the source of infection. and expression also increased in both WL and PC, although overall lower expression was observed in PC chickens at 24 h compared to 6 h. Our data suggest systemic changes in the host during early infection, indicated by the altered expression of PRs, , , , and other regulatory genes during early MDV infection. The relative expression of these responses in PC and WL chickens suggests they may play a key role in their response to natural MDV infection in the lungs and long-term pathogenesis and survival.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281646PMC
http://dx.doi.org/10.3390/v16071130DOI Listing

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