IFN-lambda 4 desensitizes the response to IFN-alpha treatment in chronic hepatitis C through long-term induction of USP18
Fan, Weiguo1; Xie, Shiqi1,5; Zhao, Xinhao1; Li, Nan1,2; Chang, Chong1; Li, Li1; Yu, Ge3; Chi, Xiumei3; Pan, Yu3; Niu, Junqi3; Zhong, Jin1; Sun, Bing1,4
2016-09
Source PublicationJOURNAL OF GENERAL VIROLOGY
ISSN0022-1317
Volume97Pages:2210-2220
Status已发表
DOI10.1099/jgv.0.000522
AbstractThe recently discovered interferon lambda 4 (IFN-lambda 4) is a new member of the human type III interferons which could induce a strong antiviral effect through the JAK-STAT cascade. However, hepatitis C virus (HCV) patients who are capable of expressing IFN-lambda 4 usually have poor response to IFN-alpha treatment, and the mechanism behind this paradox remains unknown. Here, we reported that IFN-lambda 4 desensitized IFN-alpha-stimulated JAK-STAT signalling. Microarray analysis revealed that IFN-lambda 4 could induce ubiquitin specific peptidase 18 (USP18), a known inhibitor of the type I IFN signalling pathway, in a more sustained pattern compared with type I interferon induction. Moreover, only HCV genotype 1b but not 2a replicon cells pretreated with IFN-lambda 4 had an attenuated response to type I IFN treatment, which might be due to the different level of USP18 expression. Consistently, knockdown of USP18 in HCV genotype 1b-containing replicon cells reversed the resistance induced by IFN-lambda 4 and promoted viral clearance. Finally, IFN-lambda 4 is also strongly associated with the poor response to IFN-alpha in a Chinese HCV genotype 1b cohort. In conclusion, these data indicate that IFN-lambda 4 attenuates the response of HCV genotype 1b to IFN-alpha therapy and inhibits the JAK-STAT signalling pathway by inducing USP18 expression.
Indexed BySCI
Language英语
Funding ProjectNational 973 key project[2015CB554302] ; National 973 key project[2013CB530504] ; National 973 key project[2015CB554303]
WOS Research AreaBiotechnology & Applied Microbiology ; Virology
WOS SubjectBiotechnology & Applied Microbiology ; Virology
WOS IDWOS:000385291700018
PublisherMICROBIOLOGY SOC
WOS KeywordHUMAN-LEUKOCYTE INTERFERON ; JAK-STAT PATHWAY ; VIRUS-REPLICATION ; INFECTION ; LAMBDA ; HEPATOCYTES ; CELLS ; HCV ; IDENTIFICATION ; EXPRESSION
Original Document TypeArticle
Citation statistics
Cited Times:15[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1718
Collection生命科学与技术学院
生命科学与技术学院_特聘教授组_孙兵组
生命科学与技术学院_硕士生
Corresponding AuthorNiu, Junqi; Zhong, Jin; Sun, Bing
Affiliation1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Mol Virol & Immunol,Inst Pasteur Shanghai, Shanghai 200031, Peoples R China
2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
3.Jilin Univ, Hosp 1, Hepatol Sect, Changchun 130021, Jilin, Peoples R China
4.Inst Biochem & Cell Biol, Lab Mol Cell Biol, Shanghai, Peoples R China
5.Univ Texas Southwestern Med Ctr Dallas, Dept Obstet & Gynecol, Cecil H & Ida Green Ctr Reprod Biol Sci, Dallas, TX 75390 USA
Recommended Citation
GB/T 7714
Fan, Weiguo,Xie, Shiqi,Zhao, Xinhao,et al. IFN-lambda 4 desensitizes the response to IFN-alpha treatment in chronic hepatitis C through long-term induction of USP18[J]. JOURNAL OF GENERAL VIROLOGY,2016,97:2210-2220.
APA Fan, Weiguo.,Xie, Shiqi.,Zhao, Xinhao.,Li, Nan.,Chang, Chong.,...&Sun, Bing.(2016).IFN-lambda 4 desensitizes the response to IFN-alpha treatment in chronic hepatitis C through long-term induction of USP18.JOURNAL OF GENERAL VIROLOGY,97,2210-2220.
MLA Fan, Weiguo,et al."IFN-lambda 4 desensitizes the response to IFN-alpha treatment in chronic hepatitis C through long-term induction of USP18".JOURNAL OF GENERAL VIROLOGY 97(2016):2210-2220.
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