Inhibition of hepatitis E virus replication by zinc-finger antiviral Protein synergizes with IFN-β
Wenhai Yu
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
Search for more papers by this authorHanbin Ji
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorFeiyan Long
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorShuangfeng Chen
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorQiuxia He
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorYueping Xia
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorChao Cong
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorChenchen Yang
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorDaqiao Wei
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorCorresponding Author
Fen Huang
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Yunnan Provincial Key Laboratory of Clinical Virology, Kunming, China
Correspondence
Fen Huang, Medical Faculty, Kunming University of Science and Technology, Kunming, China.
Email: [email protected]
Search for more papers by this authorWenhai Yu
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China
Search for more papers by this authorHanbin Ji
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorFeiyan Long
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorShuangfeng Chen
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorQiuxia He
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorYueping Xia
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorChao Cong
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorChenchen Yang
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorDaqiao Wei
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Search for more papers by this authorCorresponding Author
Fen Huang
Medical Faculty, Kunming University of Science and Technology, Kunming, China
Yunnan Provincial Key Laboratory of Clinical Virology, Kunming, China
Correspondence
Fen Huang, Medical Faculty, Kunming University of Science and Technology, Kunming, China.
Email: [email protected]
Search for more papers by this authorYu, Ji, Long and Chen contributed equally to this study.
Abstract
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.
CONFLICT OF INTEREST
All authors declared no conflict of interest to this manuscript.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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