Journal Article Research Support, Non-U.S. Gov't Epublish
PubMed: 40284946 DOI: 10.3390/v17040503
Cyclooxygenase-2/Prostaglandin E2 Pathway Facilitates Infectious Bronchitis Virus-Induced Necroptosis in Chicken Macrophages, a Caspase-Independent Cell Death.
Viruses 17(4)
Authors: Motamed Elsayed Mahmoud, Dylan Tingley, Akeel Faizal, Awais Ghaffar, Muhammed Azhar, Doaa Salman, Ishara M Isham, Mohamed Faizal Abdul-Careem
Affiliations
- Faculty of Veterinary Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
- Department of Animal Husbandry, Faculty of Veterinary Medicine, Sohag University, Sohag 84524, Egypt.
Abstract
Infectious bronchitis virus (IBV) poses a major challenge to poultry health and productivity. This study examined how inflammatory cell death pathways influence the replication and pathogenesis of two IBV strains-respiratory Connecticut (Conn) A5968 and nephropathogenic Delmarva (DMV)/1639-in chicken macrophages. Low serum conditions enhanced viral replication, reduced cell viability, and promoted apoptosis and necroptosis, with DMV/1639 showing more pronounced effects. Modulation of the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway displayed strain-specific effects, mitigating necroptosis in DMV/1639-infected cells but exacerbating apoptosis and necroptosis in Conn A5968-infected cells. Broad caspase inhibition (z-VAD-FMK) reduced necroptosis, while selective caspase-1/4 inhibition heightened apoptotic responses. Caspase-8 inhibition selectively reduced necroptosis in DMV/1639 infections but increased apoptosis and necroptosis in Conn A5968 infections. NLRP3 inflammasome and RIPK1 inhibition decreased cell viability and increased apoptosis in both strains but had distinct effects on necroptosis. These findings reveal the strain-specific regulation of viral replication, apoptosis, and necroptosis, underscoring the intricate interplay between IBV and host inflammatory pathways. Understanding these mechanisms provides novel insights into IBV pathogenesis and highlights potential therapeutic strategies to mitigate its impact on poultry health.
MeSH
Cells, Cyclooxygenase 2, Infectious Bronchitis Virus, Poultry, Cell Survival, Prostaglandin-Endoperoxide Synthases, Macrophages, Necroptosis, Virology, Bronchitis, Prostaglandins, Virus Replication, Caspases, Viruses, Pyroptosis, Apoptosis, Cell Death, Infections, Dinoprostone