Forsythoside A inhibits apoptosis and autophagy induced by infectious bronchitis virus through regulation of the PI3K/Akt/NF-κB pathway

Infectious bronchitis virus (IBV) causes an acute and highly infectious viral disease of chickens, which brings huge economic losses to the poultry industry. Forsythoside A (FTA) is a natural ingredient with wide pharmacological and biological activities, which has been demonstrated to have anti-IBV activities. In the present study, we found that IBV replication reached the highest level of 7.44 ± 0.11 copies/μL at 48 h post infection (hpi) and caused cytopathic effect and apoptosis in baby hamster kidney (BHK) cells. FTA pretreatment significantly inhibited IBV replication in a dose-dependent manner with an inhibition rate of up to 51.1%. In the presence of interferon deficiency, FTA pretreatment also inhibited IBV replication, indicating that the inhibition of FTA on IBV replication did not rely on the innate immune response of host cells. Additionally, we found that FTA pretreatment attenuated inflammation, apoptosis, and autophagy induced by IBV infection. UV-irradiation-inactivated IBV did not affect the viability of BHK cells, but it upregulated the expressions of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and nuclear factor kappa-B (NF-κB) proteins, suggesting that the apoptosis and autophagy induced by IBV infection were through activating the PI3K/Akt/NF-κB pathway. FTA pretreatment downregulated the PI3K/Akt/NF-κB pathway, and the PI3K activator and inhibitor were proven to show that FTA pretreatment inhibited IBV-induced apoptosis and autophagy by attenuating the PI3K/Akt/NF-κB pathway.