Japonicone V, a sesquiterpene lactone derivative from the flowers of Inula japonica, inhibits hepatitis E virus replication by targeting virus-associated autophagy

Abstract

Abstract Hepatitis E virus (HEV) is one of the major causes of acute hepatitis worldwide. Here, we investigated the role of autophagy on HEV replication and demonstrated anti-HEV effects of japonicone V, a main constituent of the flowers of Inula japonica. Results showed that HEV infection induced autophagy in Huh7 cells. Chloroquine (CQ) and 3-methyladenine (3-MA), two autophagy inhibitors inhibited HEV replication. Moreover, japonicone V suppressed HEV replication and inhibited autophagy in the HEV infectious model. CQ had additive inhibitory effects with japonicone V on HEV replication, while rapamycin, an autophagy inducer, attenuated japonicone V-mediated inhibition of HEV replication. In addition, HEV infection inhibited the PI3K/AKT/mTOR pathway; however, this effect could be alleviated by japonicone V treatment. Collectively, our findings reveal that autophagy machinery is required for HEV replication; japonicone V inhibited HEV replication by targeting the virus-associated autophagy, at least in part, through inhibition of the PI3K/AKT/mTOR pathway.