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.

猪繁殖与呼吸综合症（PRRS）仍然是导致全球养猪业遭受重大经济损失的主要动力。肺炎性损伤是感染猪的常见表现。先前的研究报道PRRS病毒（PRRSV）诱导培养细胞分泌促炎因子高迁移率族1号盒（HMGB1）。这项研究的目的是评估在体内感染的早期阶段，HMGB1的分泌是否与PRRSV诱导的肺部炎症反应有关。给三周大的仔猪接种高致病性PRRSV（HP-PRRSV）株HuN4或无毒PRRSV疫苗株CH1R。感染后7天进行尸检。结果表明，HuN4显着诱导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感染在猪中引起严重的间质性肺炎。相比之下，CH1R感染的猪患有轻度的肺部炎症，HMGB1分泌最少。此外，在肺泡巨噬细胞（PAM）和肺组织中都检测到高的HuN4病毒载量，而CH1R的病毒RNA局限于PAM。与肺炎的发展一致，HuN4诱导了PAM和肺组织中的炎性细胞因子，而它们在CH1R感染的猪中的表达只限于PAM。这些结果表明，HuN4诱导的HMGB1分泌进入BALF可能会增强肺部炎症反应并加剧肺损伤。这一发现为HP-PRRSV感染的炎症反应和发病机理提供了见识。