Upregulation of HMGB1 secretion in lungs of pigs infected by highly pathogenic porcine reproductive and respiratory syndrome virus.

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.