Cytokine storms and pyroptosis are primarily responsible for the rapid death of mice infected with pseudorabies virus

• Main Authors: Wei Sun, Shanshan Liu, Xuefei Huang, Rui Yuan, Jiansheng Yu
• Format: Article
• Language: English
• Published: The Royal Society 2021-08-01
• Series: Royal Society Open Science
• Subjects: cytokine storms; pyroptosis; pseudorabies virus
• Online Access: https://royalsocietypublishing.org/doi/10.1098/rsos.210296

Pseudorabies virus (PRV), the causative agent of Aujeszky's disease, is one of the most harmful pathogens to the pig industry. PRV can infect and kill a variety of mammals. Nevertheless, the underlying pathogenesis related to PRV is still unclear. This study aims to investigate the pathogenesis induced by PRV in a mouse model. The mice infected with the PRV-HLJ strain developed severe clinical manifestations at 36 h post-infection (hpi), and mortality occurred within 48–72 hpi. Hematoxylin-eosin staining and qRT-PCR methods were used to detect the pathological damage and expression of cytokines related to an immune reaction in brain tissue, respectively. The cytokine storms caused by IFN-α, IFN-β, TNF-α, IL-1β, IL-6 and IL-18 were related to the histopathological changes induced by PRV. This pattern of cytokine secretion depicts an image of typical cytokine storms, characterized by dysregulated secretion of pro-inflammatory cytokines and imbalanced pro-inflammatory and anti-inflammatory responses. In addition, the pyroptosis pathway was also activated by PRV by elevating the expression levels of nod-like receptor protein 3, Caspase-1, Gasdermin-D and interleukin-1β/18. These findings provide a way for further understanding the molecular basis in PRV pathogenesis.