College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou, China.
Vet Res. 2020 Apr 10;51(1):53. doi: 10.1186/s13567-020-00774-0.
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-1β (IL-1β), which is the central mediator of the inflammatory reaction. Excessive expression of IL-1β exacerbates inflammatory damage. Therefore, exploring the mechanisms underlying NDV-induced IL-1β expression can aid in further understanding the pathogenesis of Newcastle disease. Here, we showed that anti-IL-1β neutralizing antibody treatment decreased body temperature and mortality following infection with virulent NDV. We further explored the primary molecules involved in NDV-induced IL-1β expression from the perspective of both the host and virus. This study showed that overexpression of NLRP3 resulted in increased IL-1β expression, whereas inhibition of NLRP3 or caspase-1 caused a significant reduction in IL-1β expression, indicating that the NLRP3/caspase-1 axis is involved in NDV-induced IL-1β expression. Moreover, ultraviolet-inactivated GM (chicken/Guangdong/GM/2014) NDV failed to induce the expression of IL-1β. 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-1β expression. Moreover, NLRP3/caspase-1 was involved in GM RNA-induced IL-1β expression. Thus, our study elucidated the critical role of IL-1β in the pathogenesis of Newcastle disease while also demonstrating that inhibition of IL-1β via anti-IL-1β neutralizing antibodies decreased the damage associated with NDV infection; furthermore, GM RNA induced IL-1β expression via NLRP3/caspase-1.
新城疫病毒（NDV）感染会引起严重的炎症，是家禽中一种高度传染性的疾病。强毒力 NDV 株（GM）诱导大量白细胞介素-1β（IL-1β）的表达，IL-1β 是炎症反应的中心介质。IL-1β 的过度表达会加重炎症损伤。因此，探讨 NDV 诱导的 IL-1β 表达的机制有助于进一步了解新城病的发病机制。在这里，我们发现抗 IL-1β 中和抗体治疗可降低感染强毒力 NDV 后的体温和死亡率。我们进一步从宿主和病毒两个角度探讨了 NDV 诱导的 IL-1β 表达的主要分子。本研究表明，NLRP3 的过表达导致 IL-1β 的表达增加，而 NLRP3 或 caspase-1 的抑制导致 IL-1β 的表达显著减少，表明 NLRP3/caspase-1 轴参与了 NDV 诱导的 IL-1β 表达。此外，紫外线灭活的 GM（鸡/广东/GM/2014）NDV 不能诱导 IL-1β 的表达。然后，我们使用超速离心从 GM 感染的细胞培养上清液中收集病毒，提取病毒 RNA，并进一步用 GM RNA 刺激细胞。结果表明，RNA 本身就能够诱导 IL-1β 的表达。此外，NLRP3/caspase-1 参与了 GM RNA 诱导的 IL-1β 表达。因此，本研究阐明了 IL-1β 在新城病发病机制中的关键作用，同时也表明通过抗 IL-1β 中和抗体抑制 IL-1β 可减轻 NDV 感染相关的损伤；此外，GM RNA 通过 NLRP3/caspase-1 诱导 IL-1β 的表达。
