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Review
. 2024 Sep 29;16(10):1543.
doi: 10.3390/v16101543.

Research Progress into the Biological Functions of IFITM3

Qian Xie  1 , Liangliang Wang  2   3 , Xinzhong Liao  1 , Bi Huang  1 , Chuming Luo  1 , Guancheng Liao  1 , Lifang Yuan  1 , Xuejie Liu  1 , Huanle Luo  1   4 , Yuelong Shu  1   4   5
Affiliations
Review

Research Progress into the Biological Functions of IFITM3

Qian Xie et al. Viruses. .

Abstract

Interferon-induced transmembrane proteins (IFITMs) are upregulated by interferons. They are not only highly conserved in evolution but also structurally consistent and have almost identical structural domains and functional domains. They are all transmembrane proteins and have multiple heritable variations in genes. The IFITM protein family is closely related to a variety of biological functions, including antiviral immunity, tumor formation, bone metabolism, cell adhesion, differentiation, and intracellular signal transduction. The progress of the research on its structure and related functions, as represented by IFITM3, is reviewed.

Keywords: IFITM; IFITM3; function; structure.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Alignment of the amino acid sequences of the IFITM3 protein with the red dashed lines for humans, chimpanzees, and mice. (IFITM3 are derived from avian, non-avian reptiles and amphibians). The shade of color represents the level of sequence consistency, with dark gray indicating complete sequence consistency.
Figure 2
Figure 2
Molecular domains of the IFITM family proteins.
Figure 3
Figure 3
Schematic representation of the possible topology of the IFITM family. (A) Schematic diagram of the IFITM family protein type III transmembrane protein topology. (B) Schematic representation of the intramembrane topology of IFITM family molecules. (C) Schematic representation of IFITM3 protein type II transmembrane. IMD, intramembrane domain. TMD, transmembrane domain.
Figure 4
Figure 4
Possible antiviral mechanisms of IFITM3. (1) The amphipathic helical peptide (AH peptide) of IFITM3 may interact directly with cholesterol analogs to inhibit the formation of membrane fusion, thereby preventing viral entry. (2) IFITM3 may inhibit the fusion of virus and host cell membranes both by decreasing cell membrane fluidity and by stabilizing the cytoplasmic layer of the endosomal membrane to restrict viral entry from the intracellular compartment. (3) IFITM3 may interact with influenza virus haemagglutinin (HA) to reduce the optimal pH for membrane fusion, which in turn affects virus replication. (4) IFITM3 located in the lysosomal membrane may inhibit viral entry by disrupting transport processes in endosomes.
Figure 5
Figure 5
Possible mechanisms of IFITMs immunomodulatory effects. The expression of IFITMs was upregulated in a variety of immune cells upon activation. Th1 cells enhanced the immune function of eosinophils, macrophages, and Th2 cells by upregulating Tbet, stat1 IL-27, etc. Th2 cells facilitated this process by downregulating Gata3, IL-4, and IL-13. In addition, IFITM3 with a 21-amino-acid deletion at the N-terminus on the surface of B cells promotes antibody production by plasma cells to enhance humoral immunity. “↑”, increase; “↓”, decrease.
Figure 6
Figure 6
Prospects for future research directions in IFITM.
See this image and copyright information in PMC

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