IFITM1


Interferon-induced transmembrane protein 1 is a protein that in humans is encoded by the IFITM1 gene. IFITM1 has also recently been designated CD225. This protein has several additional names: fragilis, IFI17 , 9-27 and Leu13.
IFITM1 is a member of the IFITM family which is encoded by IFITM genes. The human IFITM genes locate on chromosome 11 and have four members: IFITM1, IFITM2, IFITM3 and IFITM5. While the mouse Ifitm genes locate on chromosome 7 and 16 and have six members: Ifitm1, Ifitm2, Ifitm3, Ifitm5, Ifitm6 and Ifitm7.

Molecular biology

The IFITM1 gene is located on the Watson strand of the short arm of chromosome 11 and is 3,956 bases in length. The encoded protein has 125 amino acids.
It is an intrinsic membrane protein and is predicted to cross the membrane several times.

Structure and function

IFITM proteins have a short N-terminal and C-terminal domain, two transmembrane domains and a short cytoplasmic domain. The first transmembrane domain and the cytoplasmic domain are conserved among different IFITM proteins in human and mouse. In the absence of interferon stimulation, IFITM proteins can express broadly in tissues and cell lines. In human, IFITM1, IFITM2 and IFITM3 are able to express in different tissues and cells while the expression of IFITM5 is limited to osteoblasts. The type I and II interferon induce IFITM proteins expression significantly. IFITM proteins are involved in the physiological process of immune response signaling, germ cell maturation and development.

Biochemistry

The gene is induced by interferon and the protein forms part of the signaling pathway.

Antiviral function of IFITM proteins

By using genomic screening for cellular factors which are involved in influenza A virus life cycle such as entry, replication and release, IFITM proteins have been identified as antiviral restriction factors for influenza A virus replication. Knockout IFITM3 increased influenza virus A replication and overexpression IFITM3 inhibits influenza virus A replication. In addition to replication competent influenza A virus, IFITM proteins were able to inhibit retrovirus based pseudotyped influenza A virus, indicating that IFITM protein inhibit influenza A virus at the early step of life cycle, may occur in the entry and fusion steps.
IFITM proteins also are able to inhibit several other enveloped viruses infection that belong to different virus families. These virus include flaviviruses, filoviruses coronaviruses and lentivirus. However, IFITM proteins did not affect alphaviruses, arenaviruses and murine leukaemia virus infection.
Potential mechanisms.IFITM proteins inhibit viral membrane and cellular endosomal or lyso¬somal vesicles membrane fusion by modify lipid components or fluidity. IFITM proteins blocked the creation of hemifusion between viral membrane and cellular membrane. Furthermore, IFITM proteins reduced membrane fluidity and affected membrane curvature to restrict viral membrane fusion with the cellular membrane. In addition, IFITM3 interacted with the cellular cholesterol regulatory proteins Vesicle-membrane-protein-associated protein A and oxysterol-binding protein to induce intracellular cholesterol accumulation, which in turn blocked viral membrane and vesicles membrane fusion.