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.

戊型肝炎病毒（HEV）是全球急性肝炎的主要原因之一。在这里，我们研究了自噬在戊型肝炎病毒复制中的作用，并证明了日本菊旋花的主要成分Japonicone V的抗HEV效应。结果显示，HEV感染可诱导Huh7细胞自噬。氯喹（CQ）和3-甲基腺嘌呤（3-MA）这两种自噬抑制剂可抑制HEV复制。此外，在HEV感染模型中，Japonicone V抑制了HEV复制并抑制了自噬。CQ与甲肝素V对HEV复制具有累加抑制作用，而自噬诱导剂雷帕霉素则减弱了甲乙酮V介导的HEV复制抑制作用。此外，HEV感染抑制了PI3K / AKT / mTOR途径。但是，通过Japonicone V处理可以减轻这种影响。总的来说，我们的发现表明，自噬机器是HEV复制所必需的。japonicone V通过至少部分地通过抑制PI3K / AKT / mTOR途径来靶向与病毒相关的自噬来抑制HEV复制。