Toosendanin activates caspase-1 and induces maturation of IL-1β to inhibit type 2 porcine reproductive and respiratory syndrome virus replication via an IFI16-dependent pathway

• DOI: 10.1186/s13567-022-01077-2
• Publication Date: 2022-07-29T10:04:33Z
• Authors: Mingxin Zhang; Chunni Lu; Lizhan Su; Feixiang Long; Xia Yang; Xiaofeng Guo; Gaopeng Song; Tongqing An; Weisan Chen; Jianxin Chen
• Keywords: Toosendanin (TSN); 0301 basic medicine; Veterinary sciences; Agricultural, veterinary and food sciences; Swine; Veterinary medicine; FOS: Veterinary sciences; Porcine Reproductive and Respiratory Syndrome; Virus Replication; Microbiology; Cell Line; 03 medical and health sciences; SF600-1100; Macrophages, Alveolar; Animals; caspase-1; Interleukin-1β (IL-1β); Porcine respiratory and reproductive syndrome virus; Swine Diseases; 0303 health sciences; Porcine reproductive and respiratory syndrome virus (PRRSV); Caspase 1; Triterpenes; 3. Good health; FOS: Biological sciences; inhibitory activity; gamma-interferon-inducible protein 16 (IFI16); Research Article

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent endemic swine pathogen which causes significant economic losses in the global industry. Multiple vaccines have been developed to prevent PRRSV infection. However, they provide limited protection. Moreover, no effective therapeutic drugs are yet available. Therefore, there an urgent need develop novel antiviral strategies infection transmission. Here we report that Toosendanin (TSN), tetracyclic triterpene found bark or fruits of Melia toosendan Sieb. et Zucc., strongly suppressed type 2 replication vitro Marc-145 cells ex vivo primary porcine alveolar macrophages (PAMs) at sub-micromolar concentrations. The results transcriptomics revealed TSN up-regulated expression IFI16 cells. Furthermore, silencing enhanced anti-PRRSV activity was dampened by silencing, suggesting inhibition against IFI16-dependent. In addition, showed activated caspase-1 induced maturation IL-1β IFI16-dependent pathway. To verify role infection, analyzed effect exogenous rmIL-1β on replication, significantly inhibited PAMs dose-dependent manner. Altogether, our findings indicate inhibits very low concentrations (EC 50 : 0.16–0.20 μM) may opportunities for developing agents.