IFNA13 - interferon alpha 13 |Elisa - Clia - Antibody - Protein

Background

Interferon Alpha 13 (IFN-α13) belongs to the Type I interferon family, which includes interferon-alpha (IFN-α) subtypes, interferon-beta (IFN-β), interferon-omega (IFN-ω), interferon-epsilon (IFN-ε), and others. Type I interferons play a critical role in the innate immune system, particularly in the body's response to viral infections, tumor surveillance, and modulation of immune responses. Type I interferons, including IFN-α13, are secreted by various immune cells, most notably plasmacytoid dendritic cells (pDCs), macrophages, and monocytes.

When a virus or other pathogen is detected by immune cells through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), Type I interferons are rapidly produced. These interferons initiate an antiviral state by stimulating interferon-stimulated genes (ISGs), which limit viral replication, spread, and promote the clearance of infected cells. IFN-α13 is one of the less-studied subtypes of the IFN-α family, but it is believed to share most of the same antiviral and immunomodulatory properties as its more well-known counterparts, such as IFN-α2.

Protein Structure

Primary Structure:

• The IFN-α13 gene is located on chromosome 9, within a cluster that encodes various IFN-α subtypes. Like other Type I interferons, the primary structure of IFN-α13 consists of a polypeptide chain that is approximately 165 amino acids long, with a molecular weight of around 20 kDa.
• The gene encodes a precursor protein with a signal peptide at the N-terminal region. This peptide directs the nascent protein to the secretory pathway, where it is cleaved to produce the mature, active interferon.

Secondary and Tertiary Structure:

• The mature IFN-α13 protein exhibits a helical structure, typical of the IFN-α subtypes. It consists of five major α-helices, which form a compact, bundle-like arrangement. This structural organization is essential for proper receptor binding and activation of downstream signaling pathways.
• The disulfide bonds between conserved cysteine residues help to stabilize the tertiary structure of IFN-α13, maintaining its conformation in extracellular environments and ensuring that it can bind effectively to its receptor complex.

Quaternary Structure:

• IFN-α13 functions as a monomer in its active form. Upon binding to its receptor, the interferon-alpha/beta receptor (IFNAR), it induces the dimerization of the receptor subunits, namely IFNAR1 and IFNAR2, which initiates the downstream signaling pathways.

Post-Translational Modifications:

• Like other interferons, IFN-α13 undergoes glycosylation during its synthesis. Glycosylation plays a crucial role in modulating the stability and half-life of the protein, as well as enhancing its interaction with immune cells.

Classification and Subtypes

IFN-α13 is classified within the IFN-α subtype family, a major component of the Type I interferon family. This family consists of over a dozen distinct IFN-α subtypes (such as IFN-α2, IFN-α5, IFN-α10, and others), each encoded by separate genes and showing slight variations in their amino acid sequences. Despite the sequence variations, all IFN-α subtypes share a common receptor, IFNAR, and largely perform similar biological functions.

However, these subtle differences between IFN-α subtypes may result in variations in receptor affinity, potency, and tissue-specific activities. IFN-α13 is considered less well-characterized than other subtypes, such as IFN-α2, but it is still thought to contribute significantly to the antiviral defense and immune modulation functions of the IFN-α family.

Function and Biological Significance

Antiviral Activity:

• Like all Type I interferons, IFN-α13 is critical in mounting an antiviral response. Upon viral infection, IFN-α13 is rapidly secreted by immune cells and binds to IFNAR on the surface of neighboring cells, activating the JAK-STAT signaling pathway. This leads to the transcription of interferon-stimulated genes (ISGs), which encode a variety of antiviral proteins.
• These antiviral proteins include PKR (Protein Kinase R), which inhibits viral protein synthesis; OAS (2'-5'-Oligoadenylate Synthetase), which degrades viral RNA; and Mx proteins, which block the replication of certain viruses. Collectively, these ISGs create a robust antiviral state in cells, preventing the spread of viral infections.

Immune Modulation:

• Beyond its antiviral activity, IFN-α13 plays a vital role in modulating both innate and adaptive immunity. It enhances the activity of natural killer (NK) cells, promoting their ability to lyse virus-infected and cancerous cells. Additionally, IFN-α13 promotes the differentiation of T-helper 1 (Th1) cells, which are crucial for the cell-mediated immune response.
• IFN-α13 also upregulates the expression of MHC class I molecules on the surface of infected cells, facilitating the recognition and destruction of infected cells by cytotoxic T lymphocytes (CTLs).

Antitumor Effects:

• Like other interferons, IFN-α13 has demonstrated antiproliferative and pro-apoptotic effects on tumor cells. It can inhibit cell growth and promote apoptosis, making it a potential candidate for cancer immunotherapy.
• IFN-α13 also enhances immune surveillance by increasing the activity of cytotoxic T cells and NK cells, both of which target and eliminate tumor cells.

Clinical Issues

Therapeutic Applications:

• While most clinical research has focused on IFN-α2 due to its extensive characterization and clinical use, IFN-α13 shares many of the same therapeutic potential as other IFN-α subtypes. It has potential applications in the treatment of viral infections, cancer, and autoimmune diseases.
• Viral Infections: Type I interferons are often used in the treatment of chronic viral infections such as hepatitis B and hepatitis C, with IFN-α2 being the primary subtype employed in clinical practice. While IFN-α13 may exhibit similar efficacy, its use has not been as widely studied.
• Cancer Therapy: The antiproliferative and pro-apoptotic effects of IFN-α13 suggest its potential use in cancer treatment, particularly for cancers such as melanoma, renal cell carcinoma, and leukemia. However, the clinical development of IFN-α13 as an antitumor agent remains limited compared to other interferon subtypes.

Autoimmune Diseases:

• The overproduction of Type I interferons, including IFN-α13, has been implicated in the development of autoimmune diseases such as systemic lupus erythematosus (SLE). In autoimmune conditions, excessive production of interferons leads to chronic immune activation and tissue damage.
• Conversely, IFN-α13 may also be considered as a potential treatment for autoimmune diseases like multiple sclerosis (MS) due to its immunomodulatory effects, though such applications are more commonly associated with IFN-β.

Side Effects:

• The clinical use of IFN-α13, like other interferons, can lead to side effects, which may limit its therapeutic utility. Common side effects include flu-like symptoms (e.g., fever, chills, fatigue), gastrointestinal issues, and hematologic complications (e.g., myelosuppression). Long-term use of interferons can also lead to neuropsychiatric effects, including depression and cognitive disturbances, which require careful monitoring during treatment.

Summary

Interferon Alpha 13 (IFN-α13) is a member of the Type I interferon family and contributes to the innate immune defense against viral infections and tumor cells. Structurally, it shares the typical α-helical conformation seen in other IFN-α subtypes, and it functions by binding to the IFNAR receptor to initiate antiviral and immune-modulatory signaling via the JAK-STAT pathway.

Despite its functional similarity to other well-studied interferons, such as IFN-α2, IFN-α13 has not been as extensively investigated in clinical settings. Nonetheless, its antiviral, antiproliferative, and immunomodulatory properties indicate its potential for use in treating viral infections, cancer, and possibly autoimmune disorders. However, like all interferons, the therapeutic use of IFN-α13 comes with the risk of side effects, which can limit its long-term application. Further research into IFN-α13 may provide more insights into its specific biological roles and clinical utility.