Interferons

Interferons are a group of glycoproteins important in the control of viral infections as well as other immune responses. One of their most important functions is to prepare cells in the vicinity of a virally infected cell to cease protein synthesis in the event they become infected with a virus themselves. This prevents viral replication within those neighboring cells, limiting the spread of the virus.

Cells use the presence of double-stranded RNA to indicate they have been infected with a virus. Eukaryotic cells typically do not contain double-stranded RNA because only one strand of DNA in a gene is used as a template for RNA synthesis. Replication of RNA viruses other than retroviruses, however, routinely generates double-stranded RNA. Even DNA viruses often give rise to double-stranded RNA as a consequence of their efficient use of their relatively small genomes; in some regions, both strands of DNA are transcribed into mRNA.

Double-stranded RNA in an animal cell induces the synthesis and subsequent secretion of interferon (figure 15.11). The interferon molecules then attach to a specific receptor on both the infected cell and neighboring cells, causing them to activate genes encoding enzymes capable of directing the degradation of mRNA and inhibition of protein synthesis. The action of these enzymes requires the presence of double-stranded RNA, preventing viral replication in infected cells without impacting uninfected cells. This process essentially sacrifices an infected host cell in order to prevent viral spread. Interferons provide some protection against most types of viruses.

Three types of interferon are known. One type, interferon alpha, is a family of closely related proteins produced by various white blood cells. In addition to its antiviral activity, it also contributes to fever production. A second type, interferon beta, is made by fibroblasts, which are cells of fibrous supporting tissue.

15.9 Fever 389

Virus

Virus infects cell

Virus

Virus

Virus infects cell

Virus

When viral double-stranded RNA is present, enzymes actively degrade mRNA; protein synthesis stops; cell dies and virus cannot replicate

Genes for mRNA-degrading enzymes are activated in response to signal from interferon

Cell produces virus and dies

Cell dies, but no virus is produced

Interferon attaches to receptors on cell surface

When viral double-stranded RNA is present, enzymes actively degrade mRNA; protein synthesis stops; cell dies and virus cannot replicate

Genes for mRNA-degrading enzymes are activated in response to signal from interferon

Cell produces virus and dies

Cell dies, but no virus is produced

Figure 15.11 Mechanism of the Antiviral Activity of Interferons Interferons are small glycoproteins made by virus-infected cells that act on nearby cells, causing them to produce antiviral proteins.These proteins are enzymes that inhibit virus replication in various ways.

Both alpha and beta interferons are made by many cell types when infected with viruses. A third type, inteferon gamma, is made by lymphocytes; unlike the other interferons, its synthesis is not directly related to viral infection. In addition to being antiviral, interferon gamma is very important in enhancing the killing power of macrophages, and also functions in the development and regulation of the adaptive immune response.

Interferons are quite species specific with regard to host, which initially prevented their widespread therapeutic use; interferon from other animals is not effective in humans. Microorganisms, however, have now been genetically engineered to produce human interferons. Interferon alpha has been approved in the United States for treatment of Kaposi's sarcoma in AIDS patients, chronic hepatitis B and hepatitis C infections, and several other diseases. Interferon beta is used to slow the progression of multiple sclerosis (MS), but the mechanisms of its beneficial effects are unclear. ■ genetic engineering, pp. 220,230

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