Control of Viral RNA Translation as the Mechanism of Interferon Action

One of the most remarkable molecules of bio-logical origin implicated in the control of gene expression is interferon. Discovered in 1957 by Isaacs and Lindenmann, this molecule, a slightly acidic protein with a molecular weight of about 30,000 (Merigan, 1964), is produced by the cell in response to an appropriate stimulus, usually viral nucleic acid. Interferon can induce in animal cells a state of refractoriness to infection by an enormously broad spectrum of viruses, including both RNA and DNA types. If virus infection is viewed as the introduction i to sus-ceptible cells of a new polycistronic messenger, the viral genome of RNA viruses and the tran-scribed genome of DNA viruses, then interferon presumably acts on the cell to prevent expression of most or all of the viral genome. Thus, infor-mation concerning the molecular basis of interferon action should provide insight into the basic prob-lems concerned with the expression and control of polycistronic messengers. To date, it is generally accepted that there is little or no synthesis of viral RNA in interferon-treated cells, that direct inactivation of virions or infectious RNA is not involved, and that virus attachment and engulf-ment, viral uncoating, assembly, and release are not interfered with. However, the precise mech-anism whereby interferon acts to prevent viral replication has not been elucidated (see reviews of