Abstract
Although lysine methylation is classically known to regulate histone function, its role in modulating antiviral restriction factor activity remains uncharacterized. Interferon-induced transmembrane protein 3 (IFITM3) was found monomethylated on its lysine 88 residue (IFITM3-K88me1) to reduce its antiviral activity, mediated by the lysine methyltransferase SET7. Vesicular stomatitis virus and influenza A virus infection increased IFITM3-K88me1 levels by promoting the interaction between IFITM3 and SET7, suggesting that this pathway could be hijacked to support infection; conversely, IFN-α reduced IFITM3-K88me1 levels. These findings may have important implications in the design of therapeutics targeting protein methylation against infectious diseases.
Keywords:
Antiviral Agents; Antiviral Host Restriction Factors; Host Defense; Host-pathogen Interactions; IFITM3; Lysine Methylation; Post-translational Modification; Protein Methylation; SET7.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line
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Chlorocebus aethiops
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Gene Knockdown Techniques
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HEK293 Cells
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Histone-Lysine N-Methyltransferase / antagonists & inhibitors
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Histone-Lysine N-Methyltransferase / genetics
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Histone-Lysine N-Methyltransferase / metabolism*
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Humans
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Influenza A virus / immunology
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Influenza A virus / pathogenicity
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Interferon Type I / metabolism
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Lysine / chemistry
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Membrane Proteins / chemistry*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Methylation
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Molecular Sequence Data
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Protein Processing, Post-Translational
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RNA-Binding Proteins / chemistry*
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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Signal Transduction
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Vero Cells
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Vesiculovirus / immunology
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Vesiculovirus / pathogenicity
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Virus Diseases / immunology
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Virus Diseases / metabolism
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Virus Diseases / prevention & control
Substances
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IFITM3 protein, human
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Interferon Type I
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Membrane Proteins
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RNA-Binding Proteins
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Histone-Lysine N-Methyltransferase
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SETD7 protein, human
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Lysine