Coinfection of Porcine Circovirus 2 and Pseudorabies Virus Enhances Immunosuppression and Inflammation through NF-κB, JAK/STAT, MAPK, and NLRP3 Pathways

Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are economically important pathogens in swine. PCV2 and PRV coinfection can cause more severe neurological and respiratory symptoms and higher mortality of piglets. However, the exact mechanism involved in the coinfection of PRV and PCV2 and its pathogenesis remain unknown. Here, porcine kidney cells (PK-15) were infected with PCV2 and/or PRV, and then the activation of immune and inflammatory pathways was evaluated to clarify the influence of the coinfection on immune and inflammatory responses. We found that the coinfection of PCV2 and PRV can promote the activation of nuclear factor-kappa B (NF-kappa B), c-Jun N-terminal protein kinases (JNK), p38, and nod-like receptor protein 3 (NLRP3) pathways, thus enhancing the expression of interferon-gamma (IFN-gamma), interferon-lambda 1 (IFN-lambda 1), interferon-stimulated gene (ISG15), interleukin 6 (IL6), and interleukin 1 beta (IL1 beta). Meanwhile, PCV2 and PRV also inhibit the expression and signal transduction of IFN-beta, tumor necrosis factor alpha (TNF alpha), and the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway. In addition, PCV2 and PRV infection can also weaken extracellular-signal-regulated kinase (ERK) activity. These results indicate that the regulations of cellular antiviral immune responses and inflammatory responses mediated by NF-kappa B, JAK/STAT, mitogen-activated protein kinase (MAPK), and NLRP3 pathways, contribute to immune escape of PCV2 and PRV and host antiviral responses.

Automated summary

Coinfection of PCV2 and PRV can enhance the activation of immune and inflammatory pathways, promoting the expression of interferons and interleukins while inhibiting other immune pathways. These results contribute to understanding the immune escape mechanisms of PCV2 and PRV.