Modulation of reactive oxygen species and inflammasome activation during bovine alphaherpesvirus-1 infection through synthetic immunometabolites

Bovine alphaherpesvirus-1 (BoHV-1) infection of the respiratory tract causes Infectious Bovine Rhinotracheitis (IBR) and predisposes to Bovine Respiratory Disease (BRD). There is little evidence on the mechanisms of inflammation and generation of reactive oxygen species in the respiratory tract during BoHV-1 infection, which hinders the development of prophylactic and therapeutic strategies to increase resistance to IBR and BRD. This project seeks to determine whether bHV-1 infection triggers (i) activation of the inflammasome and (ii) production of reactive oxygen species in bovine airway epithelial cells and resident alveolar macrophages. Moreover, we will evaluate whether immunomodulatory drugs can trigger antiviral and antioxidant mechanisms and limit inflammasome formation during bHV-1 infection. Our approach involves studies on primary respiratory cell cultures that recapitulate the in vivo physiology of respiratory cells that are relevant to IBR and BRD pathogenesis. Our project will shed light on IBR pathogenesis and advance immunomodulatory strategies to prevent respiratory disease in cattle.