ß-catenin facilitates fowl adenovirus serotype 4 replication through enhancing virus-induced autophagy.

ABSTRACT

ß-catenin is a key component of the Wnt/ß-catenin signal transduction cascade which is a highly conserved signaling pathway in eukaryotes. Increasing evidence suggests that the Wnt/ß-catenin signaling pathway is involved in the infection of many viruses. However, its role in fowl adenovirus serotype 4 (FAdV-4) replication remains unclear. In the present study, we showed that FAdV-4 infection increased the expression of ß-catenin and promoted the nuclear translocation of ß-catenin. Overexpression of ß-catenin and LiCl treatment stimulated the accumulation of ß-catenin in the nucleus, and then facilitated FAdV-4 replication. Conversely, repression of ß-catenin by inhibitors and siRNA significantly inhibited FAdV-4 replication. Furthermore, inhibition of autophagy by 3-Methyladenine (3-MA) suppressed the FAdV-4 replication, and repression of ß-catenin inhibited the FAdV-4-triggered autophagy. In conclusion, the nuclear translocation of ß-catenin benefits FAdV-4 replication, and suppression of ß-catenin limits FAdV-4 production by inhibiting FAdV-4-induced autophagy. These findings indicated that ß-catenin is an important regulator of FAdV-4 replication which can serve as a potential target for anti-FAdV-4 agents.