Luteolin inhibits BHV-1 replication and alleviates virus-induced inflammatory responses by regulating PI3K/AKT...

Bovine herpesvirus type 1 (BHV-1) seriously affects the production safety of the cattle industry and leads to epidemics worldwide. Luteolin (Lut), a flavonoid substance, can be found in vegetables, fruits, and herbs and possesses various biological properties. Here, we found that Lut can dose-dependently and significantly inhibit the cytopathic effects of BHV-1, decrease the viral titer, and suppress the BHV-1 gB gene and VP8 protein levels on bovine nasal turbinate osteoblasts (BT) and bovine kidney epithelial cells (MDBK). Mechanistic studies revealed that Lut can stably bind to the active sites of PI3K and AKT, and inhibit the PI3K/AKT pathway. Interestingly, 740Y-P (an agonist of the PI3K/AKT pathway) significantly attenuated the anti-BHV-1 effects of Lut. Further studies on the anti-inflammatory effects of Lut revealed that it attenuated BHV-1-induced activation of the NFκB pathway, which significantly suppressed the expression of TNF-α, IL-1β, IL-6, and IL-8 and increased the expression levels of IL-4 and IL-10. The PI3K/AKT pathway was also found to be involved in the anti-inflammatory effects of Lut. These results confirm the inhibitory effect of Lut on BHV-1 replication, which lays the foundation for further studies on the prevention and control of BHV-1.