Antiviral effect of palmatine against infectious bronchitis virus through regulation of NF-κB/IRF7/JAK-STAT signalling pathway and apoptosis

Abstract

ABSTRACT 1. Infectious bronchitis virus (IBV), a gamma-coronavirus, can infect chickens of all ages and leads to an acute contact respiratory infection. This study evaluated the anti-viral activity of palmatine, a natural non-flavonoid alkaloid, against IBV in chicken embryo kidney (CEK) cells. 2. The half toxic concentration (CC50) of palmatine was 672.92 μM, the half inhibitory concentration (IC50) of palmatine against IBV was 7.76 μM and the selection index (SI) was 86.74. 3. Mode of action assay showed that palmatine was able to directly inactivate IBV and inhibited the adsorption, penetration and intracellular replication of IBV. 4. Palmatine significantly upregulated TRAF6, TAB1 and IKK-β compared with the IBV-infected group, leading to the increased expressions of pro-inflammatory cytokines IL-1β and TNF-α in the downstream NF-κB signalling pathway. 5. Palmatine significantly up-regulated the levels of MDA5, MAVS, IRF7, IFN-α and IFN-β in the IRF7 pathway, inducing type I interferon production. It up-regulated the expression of 2’5’-oligoadenylate synthase (OAS) in the JAK-STAT pathway. 6. IBV infection induced cell apoptosis and palmatine-treatment delayed the process of apoptosis by regulation of the expression of apoptosis-related genes (BAX, BCL-2, CASPASE-3 and CASPASE-8). 7. Palmatine could exert anti-IBV activity through regulation of NF-κB/IRF7/JAK-STAT signalling pathways and apoptosis, providing a theoretical basis for the utilisation of palmatine to treat IBV infection.