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Updated: Mar 16, 2026

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Soluble IL-6 Receptor and IL-27 Subunit p28 Protein Complex Mediate the Antiviral Response through the Type III IFN
Xiaodan Yang1, Hua Hao1, Zhangchuan Xia1
1State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Abstract:
Previously, we demonstrated that the soluble IL-6R (sIL-6R) plays an important role in the host antiviral response through induction of type I IFN and sIL-6R-mediated antiviral action via the IL-27 subunit p28; however, the mechanism that underlies sIL-6R and p28 antiviral action and whether type III IFN is involved remain unknown. In this study, we constructed a sIL-6R and p28 fusion protein (sIL-6R/p28 FP) and demonstrated that the fusion protein has stronger antiviral activity than sIL-6R alone. Consequently, knockout of sIL-6R inhibited virus-triggered IFN-λ1 expression. In addition, sIL-6R/p28 FP associated with mitochondrial antiviral signaling protein and TNFR-associated factor 6, the retinoic acid-inducible gene I adapter complex, and the antiviral activity mediated by sIL-6R/p28 FP was dependent on mitochondrial antiviral signaling protein. Furthermore, significantly reduced binding of p50/p65 and IFN regulatory factor 3 to the IFN-λ1 promoter was observed in sIL-6R knockout cells compared with the control cells. Interestingly, a novel heterodimer of c-Fos and activating transcription factor 1 was identified as a crucial transcriptional activator of IFN-λ1 The sIL-6R/p28 FP upregulated IFN-λ1 expression by increasing the binding abilities of c-Fos and activating transcription factor 1 to the IFN-λ1 promoter via the p38 MAPK signaling pathway. In conclusion, these results demonstrate the important role of sIL-6R/p28 FP in mediating virus-induced type III IFN production.
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