Interferons Coordinate the Antiviral Response

INTERFERONS COORDINATE THE ANTIVIRAL RESPONSE

Interferons are a class of proteins induced in animal cells in response to virus infection. Clinical treatment with interferons is used to treat viral infections in a few cases (e.g., against hepatitis B and hepatitis C infections). Interferons α and β ( INF α and INF β ) block the spread of viruses by interfering with virus replication. (Although interferon γ shares the same name, it is quite distinct and is not induced directly by virus infection. It has a regulatory role in response to intracellular pathogens.) Interferons α and β are secreted in response to double-stranded RNA, which is symptomatic of the replication of most RNA viruses. They bind to the interferon receptors of both the infected cell itself and its neighbors. Locally, this triggers a phosphorelay signal pathway that activates several genes involved in opposing virus infection ( Fig. 22.2 ).

Antiviral proteins induced by interferon include oligoadenylate synthetase, which converts ATP into 2′-5′-linked poly(A). This removes the ATP required as an energy source for viral replication. In addition, 2′- 5′-poly(A) activates an endonuclease that cleaves viral RNA. P1 kinase is also activated and phosphorylates initiation factor eIF2, halting protein synthesis. The Mx proteins are GTPases that probably interfere with the RNA polymerases of negative-strand RNA viruses (e.g., influenza, parainfluenza). Interferons also help activate immune system cells, such as NK cells, which selectively destroy virus infected cells.

Interferon alpha was one of the first mammalian proteins to be manufactured via genetic engineering. However, its clinical effects have been disappointing except in a few cases. Modern attempts at antiviral therapy have tended to move away from interferons and toward stimulating the RNA interference system.