RT Journal Article
SR Electronic
T1 IL-27, a Cytokine, and IFN-λ1, a Type III IFN, Are Coordinated To Regulate Virus Replication through Type I IFN
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 691
OP 703
DO 10.4049/jimmunol.1300252
VO 192
IS 2
A1 Cao, Yanhua
A1 Zhang, Rui
A1 Zhang, Wei
A1 Zhu, Chengliang
A1 Yu, Yi
A1 Song, Yu
A1 Wang, Qing
A1 Bai, Lan
A1 Liu, Yingle
A1 Wu, Kailang
A1 Wu, Jianguo
YR 2014
UL http://www.jimmunol.org/content/192/2/691.abstract
AB 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.