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Regulation of the trafficking and antiviral activity of IFITM3 by post-translational modifications

Nicholas M Chesarino1, Temet M McMichael, Jacob S Yount

  • 1Department of Microbial Infection & Immunity, Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA.

Future Microbiology
|November 19, 2014
PubMed

Insights

Interferon-induced transmembrane protein 3 (IFITM3) is a key antiviral protein. Its function in restricting viral infections, like influenza, is modulated by various post-translational modifications and membrane interactions.

Area of Science:

  • Immunology and Virology
  • Cell Biology
  • Protein Biochemistry

Background:

  • Interferon-induced transmembrane protein 3 (IFITM3) is a crucial host factor for innate immunity against viral pathogens, notably influenza virus.
  • IFITM3 functions by expanding acidic endolysosomal compartments, thereby inhibiting the fusion of endocytosed viruses and promoting their degradation.

Purpose of the Study:

  • To elucidate the role of post-translational modifications (PTMs) in regulating IFITM3's antiviral activity and cellular trafficking.
  • To investigate the membrane topology of IFITM3 during its antiviral action.

Main Methods:

  • Analysis of IFITM3's interactions with viral pathogens.
  • Studies focusing on specific PTMs: S-palmitoylation, lysine ubiquitination, lysine methylation, and tyrosine phosphorylation.
  • Investigation of IFITM3 membrane localization and conformational changes.

Main Results:

  • IFITM3 antiviral activity is positively regulated by S-palmitoylation.
  • Negative regulatory mechanisms include lysine ubiquitination, lysine methylation, and tyrosine phosphorylation.
  • Evidence suggests IFITM3 adopts multiple membrane topologies, including an intramembrane domain, for its antiviral function.

Conclusions:

  • Post-translational modifications critically control IFITM3's antiviral efficacy and localization.
  • Understanding IFITM3's dynamic membrane interactions and PTMs offers insights into host-pathogen defense mechanisms.
  • IFITM3's ability to adopt distinct membrane conformations is integral to its broad-spectrum antiviral activity.
Keywords:
IFITM3antiviralintramembrane domainmethylationpalmitoylationphosphorylationpost-translational modificationubiquitination

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