IFNB1 - interferon beta 1 |Elisa - Clia - Antibody - Protein

Background

Interferon Beta 1 (IFN-β1) is a member of the Type I interferon (IFN) family, which includes various subtypes such as IFN-α, IFN-β, IFN-ε, IFN-κ, and IFN-ω. Type I interferons play a critical role in the body’s immune response, especially in antiviral defense and modulation of immune cell activity. IFN-β1 is one of the two isoforms of IFN-β, with IFN-β1 being the major biologically active form in humans.

IFN-β1 is secreted by various cells, most notably by fibroblasts and dendritic cells in response to viral infections, bacterial products, and other immune stimuli. Its primary role is to modulate the innate immune response and establish an antiviral state in cells, protecting them from viral replication and infection. Additionally, IFN-β1 influences the adaptive immune system by enhancing the activity of various immune cells, such as natural killer (NK) cells, macrophages, and T cells.

Given its broad effects on the immune system, IFN-β1 has been explored as a therapeutic agent in several clinical conditions, most notably in multiple sclerosis (MS) and certain viral infections. It has also been implicated in the regulation of inflammation and the development of autoimmune diseases.

Protein Structure

IFN-β1 is a glycoprotein composed of 166 amino acids with a molecular weight of approximately 20 kDa. Its structure shares many similarities with other Type I interferons, especially IFN-α, but it also possesses distinct features that influence its biological activities.

Primary Structure:

• The IFN-β1 gene, IFNB1, is located on chromosome 9 in the Type I interferon gene cluster. The gene is transcribed and translated into a precursor protein that includes a signal peptide. This peptide is cleaved to yield the mature protein, which is then secreted by the cell.

Secondary and Tertiary Structure:

• The secondary structure of IFN-β1 is dominated by α-helices. Like other Type I interferons, it forms a characteristic four-helix bundle, which is crucial for its interaction with the Type I interferon receptor (IFNAR).
• The three-dimensional structure of IFN-β1 is maintained by several disulfide bonds between cysteine residues. These bonds are essential for the stability of the protein and help maintain its active conformation in the extracellular environment.
• The α-helical bundle is oriented in such a way that it presents specific residues for interaction with the IFNAR receptor complex, composed of IFNAR1 and IFNAR2 subunits.

Post-Translational Modifications:

• Glycosylation is a significant post-translational modification in IFN-β1. This glycosylation occurs on asparagine residues (N-linked glycosylation), which helps in protein folding, stability, and possibly receptor binding. The glycosylation pattern can affect the pharmacokinetics of IFN-β1, influencing its half-life in circulation and its biological activity.

Classification and Subtypes

IFN-β1 belongs to the Type I interferon family, which is defined by their ability to bind the Type I interferon receptor (IFNAR). Unlike the IFN-α subtypes, which have many different isoforms encoded by separate genes, IFN-β is more conserved and primarily exists as a single biologically active subtype in humans, IFN-β1.

Although there is a less-studied isoform, IFN-β2, which refers to hepatocyte-stimulating factor (HSF) or interleukin-6 (IL-6) in older nomenclature, IFN-β1 remains the most important and widely studied isoform with direct antiviral, immunomodulatory, and therapeutic relevance.

Function and Biological Significance

IFN-β1 has multiple biological functions that can be grouped into antiviral activity, immune modulation, and inflammation regulation.

Antiviral Activity:

• IFN-β1 is best known for its antiviral effects. When cells detect viral infection, they produce IFN-β1, which then binds to the IFNAR receptor on the surface of neighboring cells. This activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, leading to the transcription of interferon-stimulated genes (ISGs).
• ISGs encode proteins that directly inhibit viral replication and spread. These include proteins such as:
• Mx GTPases, which inhibit viral entry and uncoating.
• OAS (2'-5' oligoadenylate synthetase), which activates RNase L to degrade viral RNA.
• PKR (protein kinase R), which halts protein synthesis in virally infected cells, effectively limiting viral replication.
• This broad-spectrum antiviral response protects both infected and neighboring cells, limiting the spread of the virus within tissues.

Immune Modulation:

• In addition to its antiviral activity, IFN-β1 modulates the activity of several immune cells:
• Natural killer (NK) cells are activated by IFN-β1, enhancing their ability to recognize and destroy virus-infected cells.
• Macrophages and dendritic cells are also affected, increasing their antigen-presenting ability and cytokine production, which helps shape the adaptive immune response.
• T cells, particularly Th1 cells, are influenced by IFN-β1, promoting their differentiation and enhancing the cellular immune response against intracellular pathogens such as viruses.
• B cells can also be affected, particularly in the context of autoimmune diseases, where IFN-β1 may modulate antibody production.

Regulation of Inflammation:

• IFN-β1 plays a significant role in limiting excessive inflammation. By modulating the production of pro-inflammatory cytokines, it can act as a negative regulator of immune activation. This is particularly important in preventing immune-mediated damage in chronic infections and autoimmune diseases.

Clinical Issues

Therapeutic Applications:

IFN-β1 has been widely used in clinical settings, particularly for the treatment of multiple sclerosis (MS), an autoimmune disease where the immune system attacks the central nervous system, leading to inflammation and damage to the myelin sheath of neurons.

• Multiple Sclerosis: IFN-β1 was one of the first disease-modifying therapies approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). It reduces the frequency and severity of MS relapses by modulating the immune response. While the exact mechanism in MS is not entirely understood, it is believed that IFN-β1 reduces the trafficking of immune cells into the central nervous system, modulates the production of pro-inflammatory cytokines, and promotes the production of anti-inflammatory cytokines like IL-10. This reduces inflammation and helps prevent the damage associated with MS relapses.
• Other Viral Infections: Although IFN-β1 has been considered as a therapeutic for various viral infections, including hepatitis B and hepatitis C, other interferon subtypes like IFN-α2 have been more commonly used. However, IFN-β1 was explored as a therapeutic candidate during the COVID-19 pandemic due to its ability to boost antiviral responses.

Autoimmune Diseases:

While IFN-β1 is beneficial in diseases like multiple sclerosis, excessive or dysregulated IFN-β1 production has been implicated in certain autoimmune diseases, such as systemic lupus erythematosus (SLE). In these conditions, chronic activation of Type I interferons can lead to persistent inflammation and tissue damage.

Adverse Effects:

As with other interferons, IFN-β1 therapy can be associated with a range of side effects, which include:

• Flu-like symptoms (e.g., fever, chills, muscle aches, fatigue) are common, especially at the start of therapy.
• Injection site reactions, as IFN-β1 is often administered via subcutaneous or intramuscular injections.
• Liver function abnormalities and changes in blood cell counts are possible, requiring monitoring during treatment.
• Neuropsychiatric effects, such as depression, have also been reported, especially with long-term use of IFN-β1.

Summary

IFN-β1 is a crucial member of the Type I interferon family, playing essential roles in antiviral defense, immune modulation, and the regulation of inflammation. Structurally, it is a glycoprotein with an α-helical structure stabilized by disulfide bonds and glycosylation. It signals through the IFNAR receptor, activating the JAK-STAT pathway and inducing interferon-stimulated genes that protect cells from viral infections.

Clinically, IFN-β1 is a well-established therapy for multiple sclerosis, reducing disease relapses and modulating immune activity. Its use in other diseases, such as viral infections and autoimmune conditions, is still being explored, though it holds promise in enhancing immune responses in specific contexts. However, careful management of side effects is necessary during IFN-β1 therapy, as its broad immunomodulatory effects can sometimes lead to adverse outcomes.

In summary, IFN-β1 continues to be a key player in both basic immunology and clinical practice, particularly in autoimmune and viral diseases.