Negative regulation of interferon-induced transmembrane protein 3 by SET7-mediated lysine monomethylation

Area of Science:

• Virology
• Epigenetics
• Immunology

Background:

• Lysine methylation classically regulates histone function.
• The role of lysine methylation in antiviral restriction factors is largely uncharacterized.
• Interferon-induced transmembrane protein 3 (IFITM3) is a key antiviral restriction factor.

Purpose of the Study:

• To investigate the role of lysine methylation in modulating IFITM3 antiviral activity.
• To identify the specific methylation site and the enzyme responsible for IFITM3 modification.
• To understand how viral infections and interferon signaling affect IFITM3 methylation.

Main Methods:

• Mass spectrometry to identify lysine methylation.
• Western blotting using specific antibodies for methylated IFITM3.
• Co-immunoprecipitation assays to study protein interactions.
• Viral infection models (Vesicular stomatitis virus, Influenza A virus).
• Interferon-alpha (IFN-α) treatment.

Main Results:

• IFITM3 was found to be monomethylated on lysine 88 (IFITM3-K88me1).
• This methylation, mediated by lysine methyltransferase SET7, reduces IFITM3's antiviral activity.
• Viral infections increased IFITM3-K88me1 levels by enhancing the IFITM3-SET7 interaction.
• IFN-α treatment decreased IFITM3-K88me1 levels.

Conclusions:

• Lysine methylation of IFITM3 is a novel mechanism regulating its antiviral function.
• Viruses can exploit the SET7-mediated methylation pathway to suppress IFITM3 activity.
• IFN-α counteracts viral suppression by reducing IFITM3 methylation.
• Targeting protein methylation could be a therapeutic strategy against infectious diseases.