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Antiviral Interferon
Characteristics of Interferon Interferon (IFN) are glycoproteins (proteins with attached sugar molecules) produced naturally by certain white blood and tissue cells that is used in therapy against certain viral infections and cancer. Three major types are alpha interferon, a product of lymphocytes and macrophages; beta interferon, a product of fibroblasts and epithelial cells; and gamma interferon, a product of T cells. All three classes of interferon are produced in response to viruses, RNA, immune products, and various antigens. Their biological activities are extensive. In all cases, they bind to cell surfaces and induce changes in genetic expression, but the exact results vary. In addition to antiviral effects all three IFNs can inhibit the expression of cancer genes and have tumor suppressor effects. Alpha and beta IFN stimulate phagocytes, and gamma IFN is an immune regulator of macrophages and T and B cells. The binding of a virus to the receptors of an infected cell sends a signal into the cell nucleus that activates the genes coding for interferon (figure 2). As interferon is synthesized, it is rapidly secreted by the cell into the extracellular spaces. The action of antiviral interferon is indirect; it does not kill or inhibit the virus directly. After diffusing to nearby, uninfected cells and entering them, IFN activates a gene complex that codes for another protein. This second protein, not interferon itself, interferes with the multiplication of viruses. Interferon is not virus-specific, so its synthesis in response to one type of virus will also protect against other types. Because this inhibitory protein is the direct inhibitor of viruses, it has been a valuable treatment for a number of virus infections. Figure 2. The antiviral activity of interferon. When a cell is infected, its nucleus is triggered to transcribe and translate the interferon (IFN) gene. The interferon diffuses out of the infected cell into nearby (uninfected) cells, where it enters the nucleus. Here IFN activates a gene for synthesizing a peptide that blocks viral replication. Note that the original cell is not protected by IFN and that IFN does not prevent viruses from invading the protected cells.
Interferons are also important immune regulatory cytokines that activate or instruct the development of white blood cells. For example, alpha interferon produced by T lymphocytes activates a subset of cells called natural killer (NK) cells. In addition, one type of beta interferon plays a role in the maturation of B and T lymphocytes and in inflammation. Gamma interferon inhibits cancer cells, stimulates B lymphocytes, activates macrophages, and enhances the effectiveness of phagocytosis. Two sources of interferon are currently available. The first source is from human diploid fibroblasts growing attached to a suitable surface, and the interferon produced is widely considered to be the safest available. The second source is from bacteria in which the gene for human fibroblast interferon has been inserted into a plasmid in such a manner that interferon is synthesized and can be extracted and purified (Figure 3).
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