View source for IntronA (Interferon alpha 2b)

==An overview of IntronA (Interferon alpha 2b)==

'''IntronA''', also known as''' interferon α-2b''' (IFNα2b), is a drug used in antiviral and anti-tumor therapeutic treatments <ref name="one"> doi: 10.1155/2014/970315</ref>. IFNα2b is classified as a cytokine, a secreted protein that stimulates the immune system, and is produced by T-cells in order to hinder viral infections, cancer, bacteria, or other pathogens in humans <ref name="one"> doi: 10.1155/2014/970315</ref>. 

<StructureSection load='1rh2' size='340' side='right' caption='The IntronA (Interferon-alpha 2b) human recombinant complex with Zn+2 ion (PDB code [[1rh2]])' scene=''>

== Function ==

IFNα2b is a naturally secreted protein that is produced by the human body via antigen-presenting cells (APCs) <ref name="two"> doi: 10.1089/107999099313325</ref>. When introduced to the body for treatment, IFNα2b is injected into the body subcutaneously and binds to the surface of cells <ref name="three"> https://www.merck.com/product/usa/pi_circulars/i/intron_a/intron_a_pi.pdf</ref>. 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 <ref name="three"> https://www.merck.com/product/usa/pi_circulars/i/intron_a/intron_a_pi.pdf</ref>. Specifically in viral infections and malignancy, the interferon targets CD8+ effector T cells and CD4+ immunomodulatory T cells to amplify the body’s immune response <ref name="two"> doi: 10.1089/107999099313325</ref>. It can also help induce a caspase cascade to activate cell death in virally infected and malignant cells <ref name="two"> doi: 10.1089/107999099313325</ref>. 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 <ref name="four"> PMID:
8994971 </ref>. A zinc molecule is held within each IFNα2b monomer <ref name="four"> PMID:
8994971 </ref>. There are four significant cysteine residues on IFNα2b that create two disulfide bonds <ref name="one"> doi: 10.1155/2014/970315</ref>. The first disulfide bond is between <scene name='75/756545/Cys29_cys138/1'>Cys29</scene> and <scene name='75/756545/Cys29_cys138/1'>Cys138</scene> <ref name="one"> doi: 10.1155/2014/970315</ref>. The second disulfide bond is between Cys1 and <scene name='75/756545/Cys98_disulfide/1'>Cys98</scene> <ref name="one"> doi: 10.1155/2014/970315</ref>. IFNα2b is considered a Type I interferon and recognizes interferon alpha receptors 1 and 2 located on the target protein’s surface <ref name="one"> doi: 10.1155/2014/970315</ref>. Amino acid residues on IFNα2b that participate in binding to IFNAR 1 and 2 are present on one coiled loop and four alpha helices <ref name="one"> doi: 10.1155/2014/970315</ref>. These residues include: <scene name='75/756545/Arginine_22correct/2'>Arg22</scene>, <scene name='75/756545/Leu26_scene/2'>Leu26</scene>, <scene name='75/756545/Phe27/2'>Phe27</scene>, <scene name='75/756545/Leu30_scene/1'>Leu30</scene>, <scene name='75/756545/Lys31/1'>Lys31</scene>, <scene name='75/756545/Arg33_scene/1'>Arg33</scene>, <scene name='75/756545/His34_scene/2'>His34</scene>, <scene name='75/756545/Ser68_scene/1'>Ser68</scene>, <scene name='75/756545/Thr79/1'>Thr79</scene>, <scene name='75/756545/Lys83/2'>Lys83</scene>, <scene name='75/756545/Tyr85/1'>Tyr85</scene>, <scene name='75/756545/Tyr89/1'>Tyr89</scene>, <scene name='75/756545/Arg120/1'>Arg120</scene>, <scene name='75/756545/Lys121/2'>Lys121</scene>, <scene name='75/756545/Gln124/1'>Gln124</scene>, <scene name='75/756545/Lys131/1'>Lys131</scene>, <scene name='75/756545/Glu132/1'>Glu132</scene>, <scene name='75/756545/Arg144/1'>Arg144</scene>, and <scene name='75/756545/Glu146/1'>Glu146</scene> <ref name="one"> doi: 10.1155/2014/970315</ref>. 

== Mechanism ==

There are several pathways in which IFNα2b has an effect on the target cell <ref name="one"> doi: 10.1155/2014/970315</ref>. These pathways include the caspase cascade and the JAK-STAT pathway <ref name="one"> doi: 10.1155/2014/970315</ref> <ref name="two"> doi: 10.1089/107999099313325</ref>. The caspase cascade results in apoptosis, thereby participating in both anti-viral and anti-cancer mechanisms <ref name="two"> doi: 10.1089/107999099313325</ref>. 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 <ref name="one"> doi: 10.1155/2014/970315</ref>. In the binding of IFNα2b to an IFNAR receptor, the protein JAK (a tyrosine kinase) is activated <ref name="one"> doi: 10.1155/2014/970315</ref>. JAK is phosphorylated and in turn phosphorylates the IFNAR receptors <ref name="one"> doi: 10.1155/2014/970315</ref>. The IFNAR receptors bind to STAT proteins resulting in a cascade pathway that signals the release of antiviral proteins <ref name="one"> doi: 10.1155/2014/970315</ref>. 

== Disease ==

'''Hepatitis Virus'''

''Hepatitis B''

IFNα2b treats chronic Hepatitis B (HBV) by interfering with viral DNA synthesis and enhancing the cellular immune response <ref name="seven"> doi: 10.1016/j.cld.2007.08.010</ref>. The cytokine enhances T-cell and natural killer cell activity by interacting with the infected cell’s surface <ref name="seven"> doi: 10.1016/j.cld.2007.08.010</ref>. IFNα2b also activates antiviral enzymes to inhibit proliferation of HBV <ref name="seven"> doi: 10.1016/j.cld.2007.08.010</ref>.

''Hepatitis C''

Hepatitis C (HCV) can range from acute to chronic conditions and progression occurs in more than half of these cases <ref name="five"> doi: 10.1056/NEJMoa011232</ref>. HCV attacks the liver tissues causing inflammation and cirrhosis, which can lead to chronic liver disease <ref name="five"> doi: 10.1056/NEJMoa011232</ref>. IFNα2b is used to treat the acute stage of HVC to prevent progression into the chronic disease <ref name="five"> doi: 10.1056/NEJMoa011232</ref>. IFNα2b overall reduces the viral amplification and allows T-cells to effectively respond to the infection <ref name="six"> Doi: 10.1016/j.virol.2004.04.031</ref>.

'''Cancer'''

''Multiple Myeloma''

IFNα2b has been shown to prolong patients with multiple myeloma <ref name="eight"> doi: 10.1038/sj.leu.2401039</ref>. 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 <ref name="eight"> doi: 10.1038/sj.leu.2401039</ref>. IFNα2b therapy causes tumor stabilization and prolongation of the aggressive stage of multiple myeloma with maintained therapy <ref name="eight"> doi: 10.1038/sj.leu.2401039</ref>. 

''Hairy cell Leukemia''

IFNα2b is a major treatment for patients with hairy cell leukemia <ref name="one"> doi: 10.1155/2014/970315</ref>. The disease is characterized by B cells in the blood, bone marrow, and spleen <ref name="one"> doi: 10.1155/2014/970315</ref>. Patients who receive the therapeutic treatment experience partial to complete remission <ref name="one"> doi: 10.1155/2014/970315</ref>. The treatment is especially effective because there is rarely relapse of the cancer with consistent therapy and mild side effects <ref name="one"> doi: 10.1155/2014/970315</ref>. The presence of malignant cells decreases, predominantly in the bone marrow, and hematologic levels normalized <ref name="nine"> doi: 10.1056/NEJM198401053100104</ref>

</StructureSection>
== References ==
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