title: IL-27, a cytokine, and IFN-λ1, a type III IFN, are coordinated to regulate virus replication through type I IFN.
abstract: IL-27, a member of the IL-12 family, plays a critical role in the control of innate and adaptive immune responses. IFN-λ1, a member of the type III IFN family, shows antiviral abilities. In this study, we investigated the effects of IL-27 and IFN-λ1 on the replication of hepatitis B virus (HBV), a major pathogen associated with a high risk for cirrhosis, liver failure, and hepatocellular carcinoma. We revealed that HBV infection activates IL-27 expression and IFN-λ1 production and demonstrated that viral-activated IL-27 and IFN-λ1 are coordinated to inhibit HBV replication. Initially, HBV infection upregulates IL-27 expression, which, in turn, stimulates IFN-λ1 production through regulating ERK1/2 signaling and by enhancing NF-κB nuclear translocation to bind to the IFN-λ1 promoter. Moreover, IL-27-activated IFN-λ1 upregulates IFN-λ1 receptor (IL-28R1 and IL-10Rβ) activity, resulting in the activation of the STAT1/2 pathway, which, in turn, induces the expression of IFN-stimulated genes, including IFN-inducible dsRNA-activated protein kinase, oligoadenylate synthetase 1, and IFN-induced GTP-binding protein 1 and, finally, inhibits HBV protein expression and viral capsid-associated DNA replication. More interestingly, we also revealed that type I IFN (IFN-α) is also involved in the downregulation of HBV replication mediated by IL-27. Thus, we identified a previously unknown mechanism by which IL-27 and IFN-λ1 are coordinated to regulate virus replication through type I IFN.
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China;
authors: Yanhua
authors: Y
authors: Cao
authors: Rui
authors: R
authors: Zhang
authors: Wei
authors: W
authors: Zhang
authors: Chengliang
authors: C
authors: Zhu
authors: Yi
authors: Y
authors: Yu
authors: Yu
authors: Y
authors: Song
authors: Qing
authors: Q
authors: Wang
authors: Lan
authors: L
authors: Bai
authors: Yingle
authors: Y
authors: Liu
authors: Kailang
authors: K
authors: Wu
authors: Jianguo
authors: J
authors: Wu
mesh_terms: D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000378:metabolism / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D016898:Interferon-alpha / Q000235:genetics* / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D014779:Virus Replication / Q000235:genetics*; D000095022:Interferon Lambda
chemical_list: D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D016328:NF-kappa B; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; D053701:Receptors, Interleukin-10; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579640:IFNLR1 protein, human; C494234:IRF7 protein, human; C464565:MYDGF protein, human; C494079:STAT1 protein, human; C494084:STAT2 protein, human