IFITM3

IFITM3 (Interferon-Induced Transmembrane Protein 3) is a gene encoding a protein that belongs to the interferon-induced transmembrane (IFITM) protein family. These proteins are small, highly hydrophobic, and broadly expressed transmembrane proteins. IFITM3 is involved in a variety of cellular processes, including innate immunity, cell growth, and development.

Function:

IFITM3 is a critical component of the innate immune response against a wide range of viruses. It functions by restricting viral entry into cells. Specifically, IFITM3 localizes to endosomes and lysosomes, where it inhibits the fusion of viral membranes with the host cell membrane, thereby preventing the release of the viral genome into the cytoplasm. The exact mechanism by which IFITM3 inhibits viral fusion is still under investigation, but it is thought to involve alterations in membrane fluidity or curvature.

IFITM3 has been shown to restrict the replication of several viruses, including influenza A virus, HIV-1, dengue virus, and SARS-CoV-2. The effectiveness of IFITM3 against different viruses can vary depending on the virus strain and the cellular context.

Beyond its antiviral activity, IFITM3 also plays roles in other cellular processes, such as cell growth, differentiation, and apoptosis. These functions are less well understood compared to its antiviral activity.

Gene and Protein Structure:

The IFITM3 gene is located on human chromosome 11. The gene encodes a protein of approximately 133 amino acids in humans. IFITM3 possesses two transmembrane domains and a conserved intracellular loop that is important for its antiviral activity. Post-translational modifications, such as palmitoylation, also contribute to the protein's function and localization.

Regulation and Expression:

The expression of IFITM3 is strongly induced by type I interferon (IFN-α/β). Interferon signaling activates the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, leading to the transcriptional upregulation of IFITM3. Basal levels of IFITM3 expression can also be observed in certain cell types. The level of IFITM3 expression can influence the susceptibility of cells to viral infection.

Clinical Significance:

Genetic variations in the IFITM3 gene have been associated with susceptibility to certain viral infections, particularly influenza. A single nucleotide polymorphism (SNP) in the IFITM3 gene, rs12252-C, has been linked to increased risk of severe influenza infection and hospitalization. This SNP affects the splicing of IFITM3 mRNA, resulting in a truncated protein that is less effective at inhibiting viral entry.

IFITM3 is also being investigated as a potential therapeutic target for antiviral drug development. Strategies to enhance IFITM3 expression or activity could potentially improve the host's ability to combat viral infections.