Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2018; 24(20): 2173-2180
Published online May 28, 2018. doi: 10.3748/wjg.v24.i20.2173
Effects of hepatitis E virus infection on interferon production via ISG15
Min Wang, Ying Huang, Man He, Wen-Ju Peng, De-Ying Tian
Min Wang, Man He, Wen-Ju Peng, De-Ying Tian, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Ying Huang, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510700, Guangdong Province, China
Author contributions: Wang M and Tian DY designed the research; Wang M, Huang Y, He M and Peng WJ performed the research; Tian DY contributed new reagents; Wang M and Tian DY analyzed the data; Wang M and Tian DY wrote the paper.
Supported by the National Natural Science Foundation of China, No. 81570540.
Institutional review board statement: The study was reviewed and approved by the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Institutional Review Board.
Conflict-of-interest statement: All authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: De-Ying Tian, PhD, Professor, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430030, Hubei Province, China. dytian@tjh.tjmu.edu.cn
Telephone: +86-15387019549 Fax: +86-21-64085875
Received: March 29, 2018
Peer-review started: March 30, 2018
First decision: April 11, 2018
Revised: April 19, 2018
Accepted: April 23, 2018
Article in press: April 23, 2018
Published online: May 28, 2018
Processing time: 60 Days and 2 Hours
ARTICLE HIGHLIGHTS
Research background

Hepatitis E virus (HEV) infection is one of the most common causes of acute hepatitis or sporadic acute hepatitis in the world. At least 20 million HEV infections occur annually, which may result in chronic hepatitis in immunocompromised individuals. However, the mechanism of HEV pathogenesis remains obscure.

Research motivation

Over the last decade, numerous studies have reported that interferon (IFN)-stimulated gene (ISG)15 plays a crucial role against viral infection. However, few studies have investigated the effects of HEV on ISG15.

Research objectives

In the present study, we investigated whether HEV infection could regulate the expression of ISG15 and the impact of ISG15 on IFN production during HEV infection, which is of great significance to expand our understanding of the interaction between ISG15 and HEV pathogenesis.

Research methods

In this study, C3A cells were first transfected with genotype 3 HEV RNA. The production of IFN-alpha and -beta (IFN-α/β) at different time points (0, 8, 12, 24, 48, 72 and 120 h) were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of ISG15 in HEV-infected C3A cells at different time points were tested by western blotting. Then, C3A cells were transfected with plasmid-expressing open reading frame 3 (ORF3) or control plasmids, the levels of IFN-α/β and ISG15 was evaluated, respectively. Next, the plasmid-expressing ISG15 or small interfering RNA-inhibiting ISG15 was transfected into infected C3A cells. The production of IFN-α/β was also measured by ELISA.

Research results

In this study, we demonstrated that HEV infection could enhance the production of IFN-α/β and induce elevation of the ISG15 protein. ORF3 protein may be responsible for the enhancement of IFN-α/β and ISG15 by HEV. Furthermore, ISG15 silencing enhanced the production of IFN-α/β in C3A cells. Over-expression of ISG15 resulted in the reduction of IFN-α/β in C3A cells.

Research conclusions

The findings of the present study showed that HEV could inhibit the level of type I IFN through regulating the expression of ISG15, a finding which may enhance the understanding of the interaction between ISG15 and HEV in the host innate immune response, and provide useful insight for the development of new antiviral drugs and antiviral strategies.

Research perspectives

The future research will focus on whether HEV ORF3 could regulate the egress of HEV through ISG15.