Newcastle disease virus RNA-induced IL-1? expression via the NLRP3/caspase-1 inflammasome.

ABSTRACT: Newcastle disease virus (NDV) infection causes severe inflammation and is a highly contagious disease in poultry. Virulent NDV strains (GM) induce large quantities of interleukin-1? (IL-1?), which is the central mediator of the inflammatory reaction. Excessive expression of IL-1? exacerbates inflammatory damage. Therefore, exploring the mechanisms underlying NDV-induced IL-1? expression can aid in further understanding the pathogenesis of Newcastle disease. Here, we showed that anti-IL-1? neutralizing antibody treatment decreased body temperature and mortality following infection with virulent NDV. We further explored the primary molecules involved in NDV-induced IL-1? expression from the perspective of both the host and virus. This study showed that overexpression of NLRP3 resulted in increased IL-1? expression, whereas inhibition of NLRP3 or caspase-1 caused a significant reduction in IL-1? expression, indicating that the NLRP3/caspase-1 axis is involved in NDV-induced IL-1? expression. Moreover, ultraviolet-inactivated GM (chicken/Guangdong/GM/2014) NDV failed to induce the expression of IL-1?. We then collected virus from GM-infected cell culture supernatant using ultracentrifugation, extracted the viral RNA, and stimulated the cells further with GM RNA. The results revealed that RNA alone was capable of inducing IL-1? expression. Moreover, NLRP3/caspase-1 was involved in GM RNA-induced IL-1? expression. Thus, our study elucidated the critical role of IL-1? in the pathogenesis of Newcastle disease while also demonstrating that inhibition of IL-1? via anti-IL-1? neutralizing antibodies decreased the damage associated with NDV infection; furthermore, GM RNA induced IL-1? expression via NLRP3/caspase-1.

SUBMITTER: Gao P 

PROVIDER: S-EPMC7156904 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature