IntronA (Interferon alpha 2b)

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Function

IFNα2b is a naturally secreted protein that is produced by the human body via antigen-presenting cells (APCs) ^[4]. When introduced to the body for treatment, IFNα2b is injected into the body subcutaneously and binds to the surface of cells ^[5] When this occurs, IFNα2b produces many possible outcomes. This includes inhibiting replication of viruses within virus-infected cells, suppressing cell proliferation, enhancing activity of macrophages, stimulating certain types of enzymes, and increasing lymphocytes’ specific cytotoxicity.3 Specifically, in viral infections and malignancy the interferon specifically targets CD8+ effector T cells and CD4+ immunomodulatory T cells to amplify the body’s immune response ^[4]. It can also help induce a caspase cascade to activate cell death in virally infected and malignant cells ^[4]. Overall, INFα2b is crucial for activation and regulation of the protective immune response.

Structural highlights

Each IFNα2b monomer consists of five alpha helices and five coiled loops.4 A zinc molecule is held within each IFNα2b monomer.4 There are four significant cysteine residues on IFNα2b that create two disulfide bonds ^[1]. The first disulfide bond is between Cys29 and Cys138.1 The second disulfide bond is between Cys1 and Cys98 ^[1]. IFNα2b is considered a Type I interferon and recognizes interferon alpha receptors 1 and 2 located on the target protein’s surface ^[1]. Amino acid residues on IFNα2b that participate in binding to IFNAR 1 and 2 are present on one coiled loop and four alpha helices ^[1]. These residues include: Arg22, Leu26, Phe27, Leu30, Lys31, Arg33, His34, Ser68, Thr79, Lys83, Tyr85, Tyr89, Arg120, Lys121, Gln124, Lys131 Glu132, Arg144, and Glu146 ^[1].

Mechanism

There are several pathways in that IFNα2b has an effect on the target cell ^[1]. These pathways include the caspase cascade and the JAK-STAT pathway ^{[1] [4]}. The caspase cascade results in apoptosis, thereby participating in both anti-viral and anti-cancer mechanisms ^[4]. Once IFNα2b binds to either IFNAR 1 or 2 receptors, cytochrome c and tumor necrosis alpha factor trigger the caspase cascade, which in turn signals apoptosis ^[1]. In the binding of IFNα2b to an IFNAR receptor, the protein JAK (a tyrosine kinase) is activated ^[1]. JAK is phosphorylated and in turn phosphorylates the IFNAR receptors ^[1]. The IFNAR receptors bind to STAT proteins resulting in a cascade pathway that signals the release of antiviral proteins ^[1]. This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

Disease

Hepatitis Virus

Hepatitis C

Hepatitis C (HCV) can range from acute to chronic conditions and progression occurs in more than half of these cases.5 HCV attacks the liver tissues causing inflammation and cirrhosis, which can lead to chronic liver disease.5 IFNα2b is used to treat the acute stage of HVC to prevent progression into the chronic disease.5 IFNα2b overall reduces the viral amplification and allows T-cells to effectively respond to the infection.6

Hepatitis B

IFNα2b treats chronic Hepatitis B (HBV) by interfering with viral DNA synthesis and enhancing the cellular immune response.7 The cytokine enhances T-cell and natural killer cell activity by interacting with the infected cell’s surface.7 IFNα2b also activates antiviral enzymes to inhibit proliferation of HBV.7

Cancer

Multiple Myeloma

IFNα2b has been shown to prolong patients with multiple myeloma.8 Multiple myeloma is diagnosed when multiple clones of a specific plasma cell are found or when apparent genetic mutations are affecting the cell’s normal functions.8 IFNα2b therapy causes tumor stabilization and prolongation of the aggressive stage of multiple myeloma with maintained therapy.8

Hairy cell Leukemia

IFNα2b is a major treatment for patients with hairy cell leukemia ^[1]. The disease is characterized by B cells in the blood, bone marrow, and spleen ^[1]. Patients who receive the therapeutic treatment experience partial to complete remission ^[1]. The treatment is especially effective because there is rarely relapse of the cancer with consistent therapy and mild side effects ^[1]. The presence of malignant cells decreases, predominantly in the bone marrow, and hematologic levels normalized.9