Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1.

Abstract

Effective recognition of viral infection and subsequent triggering of antiviral innate immune responses are essential for the host antiviral defense, which is tightly regulated by multiple regulators, including microRNAs. Our previous study showed that a panel of microRNAs, including miR-155, was markedly upregulated in macrophages upon vesicular stomatitis virus infection; however, the biological function of miR-155 during viral infection remains unknown. In this paper, we show that RNA virus infection induces miR-155 expression in macrophages via TLR/MyD88-independent but retinoic acid-inducible gene I/JNK/NF-κB-dependent pathway. And the inducible miR-155 feedback promotes type I IFN signaling, thus suppressing viral replication. Furthermore, suppressor of cytokine signaling 1 (SOCS1), a canonical negative regulator of type I IFN signaling, is targeted by miR-155 in macrophages, and SOCS1 knockdown mediates the enhancing effect of miR-155 on type I IFN-mediated antiviral response. Therefore, we demonstrate that inducible miR-155 feedback positively regulates host antiviral innate immune response by promoting type I IFN signaling via targeting SOCS1.

• Authors: Pin Wang, Jin Hou, Li Lin, Chunmei Wang, Xingguang Liu, Dong Li, Feng Ma, Zhugang Wang, Xuetao Cao
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 10 Pg. 6226-33 (Nov 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20937844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon Type I
• MicroRNAs
• Mirn155 microRNA, mouse
• Socs1 protein, mouse
• Suppressor of Cytokine Signaling 1 Protein
• Suppressor of Cytokine Signaling Proteins

Topics

• Animals
• Blotting, Western
• Cell Line
• Dendritic Cells (immunology, virology)
• Enzyme-Linked Immunosorbent Assay
• Feedback
• Gene Expression Regulation (immunology)
• Immunity, Innate (genetics, immunology)
• Interferon Type I (genetics, immunology, metabolism)
• Macrophages (immunology, virology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• MicroRNAs (biosynthesis, genetics, immunology)
• RNA Interference
• RNA Virus Infections (genetics, immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (genetics, immunology)
• Suppressor of Cytokine Signaling 1 Protein
• Suppressor of Cytokine Signaling Proteins (genetics, immunology, metabolism)
• Vesiculovirus (immunology)
• Virus Replication (genetics)