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Updated: Aug 23, 2025
A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
Interferon-induced transmembrane protein 3 (IFITM3) and its antiviral activity
I Jiménez-Munguía1, A H Beaven2, P S Blank1
1Section on Integrative Biophysics Division of Basic and Translational Biophysics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), MD, USA.
Abstract:
Infections caused by enveloped viruses require fusion with cellular membranes for viral genome entry. Viral entry occurs following an interaction of viral and cellular membranes allowing the formation of fusion pores, by which the virus accesses the cytoplasm. Here, we focus on interferon-induced transmembrane protein 3 (IFITM3) and its antiviral activity. IFITM3 is predicted to block or stall viral fusion at an intermediate state, causing viral propagation to fail. After introducing IFITM3, we describe the generalized lipid membrane fusion pathway and how it can be stalled, particularly with respect to IFITM3, and current questions regarding IFITM3's topology, with specific emphasis on IFITM3's amphipathic α-helix (AAH) 59V-68M, which is necessary for the antiviral activity. We report new hydrophobicity and hydrophobic moment calculations for this peptide and a variety of active site peptides from known membrane-remodeling proteins. Finally, we discuss the effects of posttranslational modifications and localization, how IFITM3's AAH may block viral fusion, and possible ramifications of membrane composition.
Insights
Interferon-induced transmembrane protein 3 (IFITM3) stalls enveloped virus entry by blocking membrane fusion. Its amphipathic α-helix is crucial for this essential antiviral activity.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Enveloped viruses require membrane fusion for cellular entry and genome delivery.
- Interferon-induced transmembrane protein 3 (IFITM3) is a key host factor with broad-spectrum antiviral activity.
- IFITM3 is known to inhibit viral fusion, but the precise mechanism remains under investigation.
Purpose of the Study:
- To elucidate the mechanism by which IFITM3 inhibits enveloped virus membrane fusion.
- To investigate the role of IFITM3's amphipathic α-helix (AAH) in its antiviral function.
- To explore the structural and biophysical properties of IFITM3 relevant to membrane fusion inhibition.
Main Methods:
- Computational analysis of peptide hydrophobicity and hydrophobic moments.
- Comparison of IFITM3 AAH with peptides from known membrane-remodeling proteins.
- Discussion of IFITM3 topology, posttranslational modifications, and membrane localization.
Main Results:
- The amphipathic α-helix (AAH) 59V-68M of IFITM3 is essential for its antiviral activity.
- Hydrophobicity and hydrophobic moment calculations provide insights into AAH's interaction with lipid membranes.
- IFITM3 likely stalls viral fusion at an intermediate stage, preventing complete pore formation.
Conclusions:
- IFITM3 inhibits viral entry by interfering with the membrane fusion process, potentially via its AAH.
- Understanding IFITM3's mechanism offers potential for developing novel antiviral strategies.
- Membrane composition and IFITM3's biophysical properties are critical factors in its antiviral efficacy.
