The Antiviral Activity of Interferon-Induced Transmembrane Proteins and Virus Evasion Strategies

• Published in: Viruses Vol. 16; no. 5; p. 734
• Main Authors: Wang, Jingjing, Luo, Yuhang, Katiyar, Harshita, Liang, Chen, Liu, Qian
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-05-2024
• Subjects: Amino acids; Animals; Antigens, Differentiation - immunology; Antigens, Differentiation - metabolism; Antiviral activity; Antiviral agents; Antiviral Agents - pharmacology; Biological response modifiers; Cell fusion; Cell membranes; Cell signaling; COVID-19; Cytokines; Glycoproteins; Host-Pathogen Interactions - immunology; Humans; IFITMs; Immune Evasion; immune modulation; Infection; Interferon; Interferons - immunology; Interferons - metabolism; Lipid composition; Membrane fusion; Membrane Proteins - immunology; Membrane Proteins - metabolism; Mortality; Proteins; Signal Transduction; Transmembrane proteins; viral glycoproteins; Viral infections; virus and cell membrane fusion; Virus Diseases - immunology; Virus Diseases - virology; virus evasion; Virus Internalization - drug effects; Viruses; Viruses - drug effects; Viruses - immunology; IFITMs; virus and cell membrane fusion; virus evasion; antiviral activity; immune modulation; viral glycoproteins
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v16050734

Interferons (IFNs) are antiviral cytokines that defend against viral infections by inducing the expression of interferon-stimulated genes (ISGs). Interferon-inducible transmembrane proteins (IFITMs) 1, 2, and 3 are crucial ISG products and members of the CD225 protein family. Compelling evidence shows that IFITMs restrict the infection of many unrelated viruses by inhibiting the virus-cell membrane fusion at the virus entry step via the modulation of lipid composition and membrane properties. Meanwhile, viruses can evade IFITMs' restrictions by either directly interacting with IFITMs via viral glycoproteins or by altering the native entry pathway. At the same time, cumulative evidence suggests context-dependent and multifaceted roles of IFITMs in modulating virus infections and cell signaling. Here, we review the diverse antiviral mechanisms of IFITMs, the viral antagonizing strategies, and the regulation of IFITM activity in host cells. The mechanisms behind the antiviral activity of IFITMs could aid the development of broad-spectrum antivirals and enhance preparedness for future pandemics.