Fowl adenovirus serotype 4 (FAdV-4) is the primary causative agent of
hepatitis-hydropericardium syndrome (HHS) causing great economic losses to the world poultry industry. The exact factors responsible for the pathogenesis of hypervirulent FAdV-4 have not been completely elucidated. Hypervirulent FAdV-4
infection induces inflammatory damages in accompany with a high level of proinflammatory
interleukin-1 beta (IL-1β) secretion in a variety of organs. Investigation of the mechanisms underlying hypervirulent FAdV-4-induced IL-1β secretion would contribute to understanding of the pathogenesis of FAdV-4. Here, we investigated whether FAdV-4
infection activates NLRP3
inflammasome in chicken macrophage cell line HD11. The results showed that stimulation of HD11 with hypervirulent FAdV-4 induced NLRP3- and Caspase-1-dependent secretion of IL-1β. Genetic knockdown of NLRP3 or Caspase-1 expression, a critical component of
inflammasome, significantly downregulated IL-1β expression, indicating that activation of the NLRP3
inflammasome contributed to the FAdV-4-induced IL-1β secretion. Moreover,
ATP signaling and
potassium efflux were involved in the process of NLRP3
inflammasome activation. Our data indicated that hypervirulent FAdV-4
infection induces the activation of NLRP3
inflammasome and followed by massive secretion of IL-1β of macrophages, which thereby contribute to the inflamed lesion of tissues.