Effects of hepatitis E virus infection on interferon production via ISG15  

作　　者：Min Wang Ying Huang Man He Wen-Ju Peng De-Ying Tian 

机构地区：[1]Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei Province,China [2]The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510700,Guangdong Province,China

出　　处：《World Journal of Gastroenterology》2018年第20期2173-2180,共8页世界胃肠病学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China,No.81570540

摘　　要：AIM To assess the effects of hepatitis E virus(HEV) on the production of type Ⅰ interferons(IFNs) and determine the underlying mechanisms.METHODS We measured the production of interferon(IFN)-alpha and-beta(-α/β) in genotype 3 HEV-infected C3 A cells at different time points(0, 8, 12, 24, 48, 72 and 120 h) by enzyme-linked immunosorbent assay(ELISA). The expression levels of IFN-stimulated gene(ISG)15 in HEVinfected C3A cells at different time points were tested by western blotting. The plasmid-expressing open reading frame 3(ORF3) or control plasmids(green fluorescent protein-expressing) were transfected into C3A cells, and the levels of IFN-α/β and ISG15 were evaluated, respectively. Furthermore, the plasmid-expressing ISG15 or small interfering RNA-inhibiting ISG15 was transfected into infected C3A cells. Then, the production of IFN-α/β was also measured by ELISA.RESULTS We showed that genotype 3 HEV could enhance the production of IFN-α/β and induce elevation of ISG15 in C3A cells. HEV ORF3 protein could enhance the production of IFN-α/β and the expression of ISG15. Additionally, ISG15 silencing enhanced the production of IFN-α/β. Overexpression of ISG15 resulted in the reduction of IFN-α/β.CONCLUSION HEV may promote production of IFN-α/β and expression of ISG15 via ORF3 in the early stages, and increased ISG15 subsequently inhibited the production of IFN-α/β.AIM To assess the effects of hepatitis E virus(HEV) on the production of type Ⅰ interferons(IFNs) and determine the underlying mechanisms.METHODS We measured the production of interferon(IFN)-alpha and-beta(-α/β) in genotype 3 HEV-infected C3 A cells at different time points(0, 8, 12, 24, 48, 72 and 120 h) by enzyme-linked immunosorbent assay(ELISA). The expression levels of IFN-stimulated gene(ISG)15 in HEVinfected C3A cells at different time points were tested by western blotting. The plasmid-expressing open reading frame 3(ORF3) or control plasmids(green fluorescent protein-expressing) were transfected into C3A cells, and the levels of IFN-α/β and ISG15 were evaluated, respectively. Furthermore, the plasmid-expressing ISG15 or small interfering RNA-inhibiting ISG15 was transfected into infected C3A cells. Then, the production of IFN-α/β was also measured by ELISA.RESULTS We showed that genotype 3 HEV could enhance the production of IFN-α/β and induce elevation of ISG15 in C3A cells. HEV ORF3 protein could enhance the production of IFN-α/β and the expression of ISG15. Additionally, ISG15 silencing enhanced the production of IFN-α/β. Overexpression of ISG15 resulted in the reduction of IFN-α/β.CONCLUSION HEV may promote production of IFN-α/β and expression of ISG15 via ORF3 in the early stages, and increased ISG15 subsequently inhibited the production of IFN-α/β.

关 键 词：open reading frame 3 interferon-stimulated gene 15 INTERFERON-ALPHA HEPATITIS E virus interferonbeta 

分 类 号：R57[医药卫生—消化系统]