IFNA14 - interferon alpha 14 |Elisa - Clia - Antibody - Protein

Background

Interferon Alpha 14 (IFN-α14) belongs to the family of Type I interferons, which are critical components of the immune system’s innate defense mechanisms, primarily involved in antiviral responses and immune regulation. Type I interferons include interferon-alpha (IFN-α), interferon-beta (IFN-β), interferon-epsilon (IFN-ε), interferon-kappa (IFN-κ), and interferon-omega (IFN-ω). Among them, IFN-α consists of several subtypes, including IFN-α14, which is encoded by distinct genes but shares substantial functional overlap with other members of the family.

When cells recognize pathogens—primarily viruses—through pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) or RIG-I-like receptors (RLRs), they induce the production and release of IFN-α subtypes, including IFN-α14. These interferons signal neighboring cells to enter an antiviral state, reducing the spread of infection. IFN-α14, similar to its related subtypes, plays an important role in modulating both innate and adaptive immune responses, influencing antiviral defense, cell growth regulation, and immune cell activation.

Protein Structure

Primary Structure:

• The IFN-α14 gene is located on chromosome 9 in humans, within a genomic region that contains several other IFN-α subtypes. The IFN-α14 protein consists of approximately 165 amino acids, with a molecular weight of around 19–22 kDa.
• The protein contains a signal peptide at its N-terminal end, which directs it to the secretory pathway. Once this signal peptide is cleaved, the mature protein is released and exerts its biological functions.

Secondary and Tertiary Structure:

• The mature IFN-α14 protein adopts a predominantly α-helical structure, a hallmark feature of all Type I interferons. Its three-dimensional conformation consists of five or six α-helices arranged in a bundle-like formation. This compact structure is essential for its interaction with its receptor.
• Disulfide bonds between conserved cysteine residues help stabilize the protein's structure, contributing to its stability and proper folding in extracellular environments. These bonds are crucial for maintaining the integrity of the protein, allowing it to efficiently bind to its receptor and initiate signaling.

Quaternary Structure:

• Like other IFN-α subtypes, IFN-α14 functions as a monomer. It binds to a heterodimeric receptor complex composed of two subunits: IFNAR1 and IFNAR2. The interaction of IFN-α14 with this receptor is critical for triggering downstream immune signaling pathways.

Post-Translational Modifications:

• IFN-α14, like other Type I interferons, may undergo glycosylation during processing. Glycosylation helps to enhance its stability, prolong its half-life in circulation, and modulate its interactions with other cells.

Classification and Subtypes

IFN-α14 is one of the many IFN-α subtypes, which belong to the Type I interferon family. The interferon family is categorized based on their receptor specificity and biological functions. Type I interferons, including IFN-α, IFN-β, IFN-ω, IFN-ε, and IFN-κ, signal through the IFNAR receptor complex, while Type II interferon (e.g., IFN-γ) uses a different receptor and serves distinct immunological functions.

Although all IFN-α subtypes bind to the same IFNAR receptor complex, they exhibit subtle differences in receptor affinity and biological activity, which may result in tissue-specific responses and variations in antiviral potency. IFN-α14, like other subtypes, shares a high degree of sequence homology with other IFN-α members, but unique amino acid variations may confer specific functional differences. These differences are underexplored relative to better-characterized subtypes, such as IFN-α2.

Function and Biological Significance

Antiviral Activity:

• Like all Type I interferons, IFN-α14 exerts potent antiviral effects. Upon viral infection, IFN-α14 is secreted by infected cells and immune cells, particularly plasmacytoid dendritic cells (pDCs). The released IFN-α14 binds to the IFNAR receptor complex on neighboring cells, triggering the JAK-STAT signaling pathway.
• This signaling cascade leads to the transcription of numerous interferon-stimulated genes (ISGs), which encode proteins that restrict viral replication, such as Mx proteins (which inhibit viral entry), PKR (Protein Kinase R) (which blocks viral protein synthesis), and OAS (2'-5'-Oligoadenylate Synthetase) (which degrades viral RNA). Through these mechanisms, IFN-α14 contributes to establishing an antiviral state within cells and limits the spread of infection.

Immune Modulation:

• Beyond its antiviral role, IFN-α14 significantly modulates both innate and adaptive immune responses. It enhances the activity of natural killer (NK) cells and macrophages, boosting their ability to eliminate virus-infected or malignant cells.
• IFN-α14 also promotes the differentiation and activation of T-helper 1 (Th1) cells, which are key players in cell-mediated immunity. This function is critical for orchestrating immune responses against intracellular pathogens, such as viruses, and in some cases, tumor cells.
• Another key function of IFN-α14 is its ability to increase the expression of major histocompatibility complex (MHC) class I molecules on infected cells. This upregulation enhances the recognition of infected or abnormal cells by cytotoxic T lymphocytes (CTLs), which then target and eliminate these cells.

Antiproliferative and Antitumor Activity:

• IFN-α14, like other IFN-α subtypes, has demonstrated antiproliferative properties, making it a potential candidate for cancer therapy. It can inhibit cell growth and induce apoptosis (programmed cell death) in certain cancer cells, as well as enhance immune surveillance by activating cytotoxic immune cells, such as CTLs and NK cells, to target tumors.
• The antitumor effects of IFN-α14 may vary depending on the type of cancer and the tumor microenvironment, but the cytokine's role in boosting immune-mediated killing of tumor cells highlights its potential therapeutic utility.

Clinical Issues

Therapeutic Applications:

• Most clinical applications of IFN-α are focused on subtypes like IFN-α2, which have been extensively studied and approved for treating a variety of conditions, including hepatitis B, hepatitis C, and certain cancers like hairy cell leukemia and melanoma. Although IFN-α14 shares many biological properties with these subtypes, it has not been widely tested in clinical trials.
• Viral Infections: The antiviral properties of IFN-α14 suggest it could be useful in treating viral infections such as chronic hepatitis B or hepatitis C, much like IFN-α2. However, due to the focus on more established interferons, clinical research on IFN-α14 remains limited.
• Cancer Therapy: Given its antiproliferative and immune-activating properties, IFN-α14 may also have potential in cancer immunotherapy. While some IFN-α subtypes are already used in treating certain cancers, IFN-α14’s specific role in tumor biology is still under investigation.

Autoimmune and Inflammatory Diseases:

• Type I interferons, including IFN-α14, can be involved in autoimmune diseases such as systemic lupus erythematosus (SLE). In SLE and related disorders, excessive production of Type I interferons leads to chronic immune activation and tissue damage. Consequently, there is interest in understanding the precise contributions of different IFN-α subtypes, including IFN-α14, to autoimmune pathogenesis.

Side Effects:

• Similar to other Type I interferons, the therapeutic use of IFN-α14 is associated with several side effects, which may limit its application. Common side effects include flu-like symptoms (fever, chills, fatigue), gastrointestinal disturbances, and hematologic abnormalities (such as anemia or leukopenia). More severe complications, including neuropsychiatric symptoms (such as depression or cognitive dysfunction), have been observed with long-term interferon therapy, necessitating careful monitoring of patients.

Summary

Interferon Alpha 14 (IFN-α14) is a Type I interferon that plays an essential role in the body’s innate immune defense against viral infections, while also contributing to immune regulation, antitumor immunity, and inflammatory responses. Structurally, it shares a typical α-helical conformation common to Type I interferons and functions as a monomer, interacting with the IFNAR receptor complex to initiate signaling pathways that induce an antiviral state and regulate immune cell activity. Although its therapeutic applications are not as well explored as other subtypes like IFN-α2, IFN-α14 holds promise for potential applications in viral therapy and cancer immunotherapy. The involvement of interferons, including IFN-α14, in autoimmune diseases and the associated side effects of interferon therapy remain important areas for further research.