Fowl adenovirus serotype-4 induces autophagy via the AMPK-mTOR signaling pathway during viral invasion of host cells

Fowl adenovirus serotype 4 (FAdV-4) is the primary pathogen responsible for avian hepatitis-hydropericardium syndrome (HHS), which poses a significant threat to the poultry industry. Currently, the routes of FAdV-4 invasion into host cells and the related miRNA expression profiles have been elucidated, but the alterations in intracellular host factors and related signaling pathways during the FAdV-4 invasion phase remains poorly understood. Here, we identified changes in host factors through transcriptome sequencing, revealing 1,135 differentially expressed genes (DEGs) during FAdV-4 invasion, of which 647 were up-regulated and 488 were down-regulated. Analysis of the transcriptome data indicated that signaling pathways such as Wnt signaling pathway, AMPK signaling pathway, and autophagy were closely related to FAdV-4 invasion. Furthermore, we demonstrated that FAdV-4 induced autophagy via the AMPK-mTOR signaling pathway during the viral invasion phase and identified the Penton protein as a key component in inducing this process. Additionally, the activation of autophagy significantly facilitated FAdV-4 invasion, whereas autophagy inhibition markedly impaired viral invasion. Collectively, these findings will advance our knowledge of the pathogenesis of FAdV-4 infection.