Mir-302c mediates influenza A virus-induced IFNβ expression by targeting NF-κB inducing kinase

Shulin Gui; Xueyuan Chen; Mo Zhang; Fanpeng Zhao; Yushun Wan; Li Wang; Gang Xu; Li Zhou; Xin Yue; Ying Zhu; Shi Liu

doi:10.1016/j.febslet.2015.11.011

Mir-302c mediates influenza A virus-induced IFNβ expression by targeting NF-κB inducing kinase

FEBS Lett. 2015 Dec 21;589(24 Pt B):4112-8. doi: 10.1016/j.febslet.2015.11.011. Epub 2015 Nov 19.

Authors

Shulin Gui¹, Xueyuan Chen², Mo Zhang³, Fanpeng Zhao⁴, Yushun Wan⁵, Li Wang⁶, Gang Xu⁷, Li Zhou⁸, Xin Yue⁹, Ying Zhu¹⁰, Shi Liu¹¹

Affiliations

¹ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
² State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
³ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
⁴ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
⁵ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
⁶ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
⁷ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
⁸ Animal Biosafety Level III Laboratory at the Center for Animal Experiment, State Key Laboratory of Virology, Wuhan University, Wuhan 430071, China. Electronic address: [email protected].
⁹ Clinical Research Center, Wuhan Children's Hospital, Wuhan 430016, China. Electronic address: [email protected].
¹⁰ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
¹¹ State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].

PMID: 26602079
DOI: 10.1016/j.febslet.2015.11.011

Abstract

Little is known about the role of microRNA during influenza A virus (IAV) infection. We observed that NIK 3'UTR luciferase activity was elevated during IAV infection. Further studies demonstrated that miR-302c reduced NIK expression, resulting in the reduction of IFNβ mRNA expression. We found that miR-302c prevented the translocation of NF-κB from the cytosol to the nucleus. Furthermore, IAV infection downregulated miR-302c expression, leading to the activation of IFNβ expression and the inhibition of viral replication. Compared to miR-302c, miR-520e cannot promote viral replication and production, although the two microRNAs target the same site of the NIK 3'UTR. Collectively, our work defines a novel signaling pathway implicated in the control of IFNβ mRNA expression during IAV infection.

Keywords: Influenza A virus; Innate immune; MiR-302c; NF-κB-inducing kinase; Type I IFN.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions
Active Transport, Cell Nucleus
Cell Line, Tumor
Enzyme Repression
Gene Expression Regulation
Host-Pathogen Interactions
Humans
Immunity, Innate*
Immunity, Mucosal*
Influenza A Virus, H3N2 Subtype / immunology*
Influenza A Virus, H3N2 Subtype / physiology
Interferon Regulatory Factor-3 / antagonists & inhibitors
Interferon Regulatory Factor-3 / genetics
Interferon Regulatory Factor-3 / metabolism
Interferon Regulatory Factor-7 / antagonists & inhibitors
Interferon Regulatory Factor-7 / genetics
Interferon Regulatory Factor-7 / metabolism
Interferon-beta / agonists
Interferon-beta / antagonists & inhibitors*
Interferon-beta / genetics
Interferon-beta / metabolism
MicroRNAs / metabolism*
NF-kappa B / agonists
NF-kappa B / antagonists & inhibitors
NF-kappa B / metabolism
NF-kappaB-Inducing Kinase
Protein Serine-Threonine Kinases / antagonists & inhibitors*
Protein Serine-Threonine Kinases / metabolism
RNA, Messenger / metabolism
Respiratory Mucosa / enzymology
Respiratory Mucosa / immunology*
Respiratory Mucosa / metabolism
Respiratory Mucosa / virology
Response Elements
Signal Transduction
Virus Replication

Substances

3' Untranslated Regions
IRF3 protein, human
IRF7 protein, human
Interferon Regulatory Factor-3
Interferon Regulatory Factor-7
MIRN302A microRNA, human
MIRN520 microRNA, human
MicroRNAs
NF-kappa B
RNA, Messenger
Interferon-beta
Protein Serine-Threonine Kinases