Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
Shandong Binzhou Animal Science and Veterinary Medicine Academy, Binzhou, Shandong, China.
Vet Microbiol. 2021 Jan;252:108922. doi: 10.1016/j.vetmic.2020.108922. Epub 2020 Nov 5.
Porcine reproductive and respiratory syndrome (PRRS) remains a major driver for substantial economic losses to the swine industry across the world. Pulmonary inflammatory injury is a common manifestation in infected pigs. Previous studies reported that PRRS virus (PRRSV) induces secretion of high mobility group box 1 (HMGB1), a proinflammatory factor, in cultured cells. The objective of this study was to evaluate whether HMGB1 secretion is associated with PRRSV-induced pulmonary inflammatory responses in the early stage of infection in vivo. Three-week-old piglets were inoculated with either HuN4, a highly pathogenic PRRSV (HP-PRRSV) strain, or CH1R, an avirulent PRRSV vaccine strain. Necropsy was performed at 7 days post-infection. The results showed that HuN4 significantly induced the secretion of HMGB1 and inflammatory cytokines (IL-1β, IL-6) into the bronchoalveolar lavage fluid (BALF). HuN4 infection induced severe interstitial pneumonia in the pigs. In contrast, pigs infected by CH1R had mild lung inflammation with minimal HMGB1 secretion. In addition, high viral load of HuN4 was detected in both pulmonary alveolar macrophages (PAMs) and lung tissue, whereas viral RNA of CH1R was confined to PAMs. In consistent with the pneumonia development, HuN4 induced inflammatory cytokines in both PAMs and lung tissue, while their expression in CH1R-infected pigs confined only to PAMs. These results indicate that the HuN4-induced HMGB1 secretion into BALF may enhance the pulmonary inflammatory response and exacerbate the lung injury. This finding provides insights to the inflammatory response and pathogenesis of the HP-PRRSV infection.
猪繁殖与呼吸综合征（PRRS）仍然是全球养猪业遭受重大经济损失的主要原因。肺部炎症损伤是感染猪的常见表现。先前的研究报告称，猪繁殖与呼吸综合征病毒（PRRSV）在培养细胞中诱导高迁移率族蛋白 B1（HMGB1）的分泌，HMGB1 是一种促炎因子。本研究旨在评估 PRRSV 感染体内早期 HMGB1 分泌是否与肺部炎症反应有关。将 3 周龄仔猪接种高致病性 PRRSV（HP-PRRSV）毒株 HuN4 或弱毒 PRRSV 疫苗株 CH1R。感染后 7 天剖检。结果表明，HuN4 显著诱导 HMGB1 和炎性细胞因子（IL-1β、IL-6）分泌到支气管肺泡灌洗液（BALF）中。HuN4 感染引起仔猪严重间质性肺炎。相比之下，感染 CH1R 的仔猪肺部炎症较轻，HMGB1 分泌较少。此外，HuN4 在肺泡巨噬细胞（PAMs）和肺组织中均检测到高病毒载量，而 CH1R 的病毒 RNA 仅局限于 PAMs。与肺炎发展一致，HuN4 在 PAMs 和肺组织中诱导炎性细胞因子，而在感染 CH1R 的猪中仅局限于 PAMs。这些结果表明，HuN4 诱导的 HMGB1 分泌到 BALF 中可能增强肺部炎症反应并加重肺损伤。这一发现为了解 HP-PRRSV 感染的炎症反应和发病机制提供了线索。
