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

Abstract

ABSTRACT 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. IMPORTANCE Infectious bronchitis virus (IBV) is an acute and highly infectious viral disease that seriously endangered the development of the chicken industry. However, due to the limited effectiveness of commercial vaccines, there is an urgent need to develop safe and effective anti-IBV drugs. Forsythoside A (FTA) is a natural ingredient with wide pharmacological and biological activities, and it has been shown to have antiviral effects against IBV. However, the antiviral mechanism of FTA is still unclear. In this study, we demonstrated that FTA can inhibit cell apoptosis and autophagy induced by IBV infection by regulating the PI3K/AKT/NF-κB signaling pathway. This finding is important for exploring the role and mechanism of FTA in anti-IBV infection, indicating that FTA can be further studied as an anti-IBV drug.

Keywords

• Infectious bronchitis virus
• forsythoside A
• apoptosis
• autophagy
• PI3K/Akt/NF-κB signaling pathway