Interferons

Interferons

	Interferons Interferon is most optimistic approach for antiviral therapy. They were first discovered by Isaacs in 1957. Isaacs and his co workers had incubated the chorioallaootic membrane from embryonated chicken eggs in a suspension of heat killed influenza virus and then transferred this membrane to buffer. After storage for 24 hr. the membranes were discarded and the buffer tested for anti viral activity. This was done by placing a fresh piece of membrane in the buffer and then challenging the membrane with active influenza virus.
The treated membrane did not support the growth of active virus whereas untreated one (not incubated in heat-killed viral suspension) did so. It was therefore concluded that an extracellular product had been liberated in response to viral infection and this substance was named interferon. Interferon is a group of over 20 substances designated as alpha, beta and gamma interferons. Each group has many members, all proteins. They are produced by body cells in response to infection by virus. They trigger a reaction that protects against the stimulating virus as well as many other viruses. Human, interferon works only in humans. Unlike antibodies, interferons do not react with, viruses but with the cell they protect. Thus, they have broader inhibitory effect. Interferons are produced when viral genome is introduced into cell . The foreign material (perhaps a double stranded RNA) induces the cell to synthesise and secrete interferons. These bind to specific receptor sites on the surfaces of adjacent cells and trigger the production of several proteins within these cells: The proteins inhibit viral replication whose mechanism is not completely understood. Many persons believe that at least one protein binds to messenger RNA molecules coded by the virus.
In 1980 a breakthrough came in interferon research when Swiss and Japanese scientists deciphered the genetic code for interferon, and spliced E. coli plasmids with the DNA code. Experiments showed that interferon from bacterial factories would reduce hepatitis symptoms, diminish the spread of herpes zoster, and shrink certain cancers. In 1984, a Swiss biotechnology firm received a patent for alpha interferon and began marketing its product using the trade name intron. In 1986, the U.S. food & Drug Administration approved the sale of alpha interferon for use against a form of-leukemia. Alpha-and B-interferons are similar, the former synthesised by lymphoblastoid cells and the latter (discovered by Isaacs) by fibroblastic cells, macrophages and others.
Both are stimulated by replicating or abortively replicating virus. yinterferon is released by stimulation of T cells by the antigen for which they are specific, i.e. it is a Iymphokine. The interferons are present, like other chemical messengers of the body, in very small amounts. They have been purified and shown to be glycoproteins with carbohydrate groups which are essential for their activity. Through genetic engineering, however, several milligrams of interferon can be produced by expressing cloned interferon genes in eukaryotic cells, usually yeast.
	The anti viral activity of interferons can be measured by inhibition of the incorporation of radioactive uridine into viral RNA in cells infected by a togavirus. Activity is expressed in terms of the amount of interferon required to reduce the normal level of viral RNA by 50% and this is arbitrarily defined as one unit. Purified interferon has a high activity of around 10⁹ units per mg of protein. which is of the same order as the hormones. The sequences of α, β and γ interferons has been determined through cloning. This has been shown that £ and 6 interferon have basic similarity (40% homology), and both are different from y interferon. In human genome, Band y interferons are represented by a single sequence, whereas at least 12 γ interferons differing in sequence are present. Interferon enhances the activation of natural killer *(NK) cells**.

Inhibits cell division of tumor cells and is also 'a macrophage activating factor (MAF). In addition interferons can serve both positive and negative regulatory controls in the expression of immune responses. One very important effect is to control the expression of MHC antigens on the cell surface and hence influence the activity of cytotoxic and delayed type hypersensitivity T cells.
(*NK) cells play a role against virus infection. These cells arise early, with in 2 days of infection. They are not armed with antibody (unlike macreophages). They are shown to exhibit on their surface small amounts of charcteristic T0cell antigen.

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