IFITM1 gene

The IFITM1 gene (IFITM1 stands for: Interferon Induced Transmembrane Protein 1) is a protein-coding gene located on chromosome 11p15.5. The interferon-induced transmembrane protein IFITM1 (and IFITM3) encoded by the IFITM1 gene plays a role in RNA viral restriction as well as in the progression of malignant tumor entities in humans. An important paralog of this gene is IFITM3.

The IFN-induced antiviral protein restricts the entry of various viral pathogens into the cell. It prevents subsequent viral fusion and the release of viral contents into the cytosol. The IFITM1 protein is active against several viruses, including influenza A virus, SARS coronaviruses (SARS-CoV and SARS-CoV-2), Marburg virus (MARV), Ebola virus (EBOV), dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) (Narayana SK et al. 2015).

The protein is also involved in cell adhesion and the control of cell growth and migration (Shi G et al. 2021). Inhibits SARS-CoV-2 S protein-mediated syncytia formation (Buchrieser J et al. 2020). Plays a key role in the antiproliferative effect of IFN-gamma by either inhibiting ERK activation or arresting cell growth in G1 phase in a p53-dependent manner. The protein acts as a positive regulator of osteoblast differentiation. In hepatocytes, IFITM proteins act in a coordinated manner to limit HCV infection by targeting the endocytosed HCV virus for lysosomal degradation. IFITM2 and IFITM3 exhibit anti-HCV activity that may complement the anti-HCV activity of IFITM1 by inhibiting the late stages of HCV entry, possibly in a coordinated manner by trapping the virion in the endosomal pathway and targeting it for degradation in the lysosome (Narayana SK et al. 2015).

Interferon-inducible transmembrane proteins (IFITM) are a family of small homologous proteins localized in the plasma and endolysosomal membranes that confer cellular resistance to many viruses. In addition, different members of the IFITM family have been ascribed distinct functions, including germ cell specification (IFITM1-IFITM3), osteoblast function and bone mineralization (IFITM5), and immune functions (IFITM1-3, IFITM6). IFITM1-3 are expressed by T cells and are directly involved in adaptive immunity, regulating the differentiation of CD4+ T helper cells in a T cell-intrinsic manner. The interferon-inducible transmembrane proteins belong to the CD225 superfamily.

1. Buchrieser J et al. (2020) Syncytia formation by SARS-CoV-2-infected cells. EMBO J 39:e106267.
2. Gómez-Herranz M et al. (2019) The effects of IFITM1 and IFITM3 gene deletion on IFNγ stimulated protein synthesis. Cell Signal 60:39-56.
3. Narayana SK et al. (2015) The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 Inhibit Hepatitis C Virus Entry. J Biol Chem 290:25946-2559.
4. Shi G et al. (2021) Opposing activities of IFITM proteins in SARS-CoV-2 infection. EMBO J 40:e106501.