Abstract
The innate immune system plays a critical role in the initial antiviral response. However, the timing and duration of these responses must be tightly regulated during infection to ensure appropriate immune cell activation and anti-viral defenses. Here we demonstrate that during antiviral response, a negative regulator miR-221 was also induced in an ELF4-dependent manner. We further show that ELF4 promotes miR-221 expression through direct binding to its promoter. Overexpression and knockdown assay show that miR-221 can negatively regulate IFNβ production in time of virus infection. RNA-seq analysis of miR-221 overexpressed cells revealed multiple candidate targets. Taken together, our study identified a novel negative microRNA regulator of innate antiviral response, which is dependent on ELF4.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antagomirs / metabolism
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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Down-Regulation
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HEK293 Cells
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Herpesvirus 1, Human / physiology
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Humans
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Immunity, Innate / genetics*
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Interferon-beta / genetics
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Interferon-beta / metabolism
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Macrophages / immunology
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Macrophages / metabolism
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Macrophages / virology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Promoter Regions, Genetic
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Protein Serine-Threonine Kinases / genetics
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Rhabdoviridae Infections / immunology*
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Rhabdoviridae Infections / pathology
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Rhabdoviridae Infections / virology
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Vesiculovirus / genetics
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Vesiculovirus / immunology
Substances
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Antagomirs
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DNA-Binding Proteins
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Elf4 protein, mouse
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MIRN221 microRNA, mouse
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MicroRNAs
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Transcription Factors
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Interferon-beta
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Tbk1 protein, mouse
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Protein Serine-Threonine Kinases