Inhibition of hepatitis E virus replication by zinc‐finger antiviral Protein synergizes with IFN‐β

• Published in: Journal of viral hepatitis 2021-08, Vol.28 (8), p.1219-1229
• Main Authors: Yu, Wenhai, Ji, Hanbin, Long, Feiyan, Chen, Shuangfeng, He, Qiuxia, Xia, Yueping, Cong, Chao, Yang, Chenchen, Wei, Daqiao, Huang, Fen
• Format: Article
• Language: English
• Subjects: Genotypes; Hepatitis; hepatitis E virus; IFN‐β; Infections; Interferon; Interferon regulatory factor 3; Life cycles; Phosphorylation; Polyinosinic:polycytidylic acid; Replication; RNA-mediated interference; Viruses; Zinc finger proteins; zinc‐finger antiviral viral protein
• ISSN: 1352-0504; 1365-2893
• DOI: 10.1111/jvh.13522

Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide. However, host–HEV interactions have yet to be fully understood. Zinc‐finger antiviral protein (ZAP) is a novel interferon (IFN)‐stimulated gene product that inhibits a variety of viruses in synergy with IFN‐β. To evaluate the role of ZAP in HEV infection, its expressions in HEV‐infected patients and in cell cultures were measured. We report a significant inhibition of ZAP expression in patients with HEV genotype four acute infection. The expression of ZAP in the HEV life cycle was monitored in cultures of HEV‐infected cells. Results indicated that the ZAP level decreased significantly after HEV infection. ZAP over‐expression inhibited HEV replication, whereas its knockdown by RNA interference significantly increased HEV RNA. These suggest that ZAP serves as an antiviral in HEV infection. Moreover, silencing ZAP decreased IFN regulatory factor 3 (IRF3) phosphorylation in HEV‐infected cells treated with poly(I:C), indicating that ZAP synergizes with IFN‐β. In conclusion, ZAP is an important anti‐HEV host factor and in synergy with IFN‐β, inhibits HEV replication.