National Institute for Medical Research

Date:: 1968

Reference:: PP/CRI/E/1/17/2

Catalogue details

Licence: In copyright

Credit: National Institute for Medical Research. Source: Wellcome Collection.

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Interferon Production One of the most striking features about interferon production is the wide variety of agents that will induce the process. These include viruses, nucleic acids, synthetic polyanions, bacterial endotoxins, bacteria and protozoa. It is this very complexity that makes unification of ideas difficult. Upon stimulation, most tissue culture'cells will Droduce interferon, as will most animals. The inducers can be divided into three broad groups. 1. Viruses . (a) In tissue culture . Both live and inactivated viruses produce interferon in tissue culture by a process which requires RNA and protein synthesis. The inhibition by very low doses of actinomycin and the species specificity of most interferons indicate that production involves the activation of the cellular genome, and this has often been pictured as operating by a process similar to bacterial derepression. The inducer of the process is probably the viral nucleic acid and until recently it was thought that the first step in virus induced interferon formation was the formation of a double-stranded RMA molecule which interacted, either direcly or indirectly, with the host genome. However, several observations indicate that this is an over simplification: (i) Use of temperature sensitive mutants of Tindbis and Semliki forest viruses has shown that formation of double-stranded viral RNA is not sufficient per se for interferon production, which presumably depends upon some further stage in the virus multiplication cycle. (ii) Interferon is produced by ultra-violet inactivated influenza viruses under conditions where RNA synthesis is unlikely, and it is probable that the inducer is the parental RNA molecule. (iii) Interferon production induced by DNA viruses cannot proceed through double-stranded RNA. It has been observed that adenovirus-induced interferon production is sensitive to trypsin treatment of the virus. No explanation of this observation can yet be given. (b) In animals Viruses induce interferon formation in animals by two processes - one of which resembles the process operating in tissue culture, while the other operates by a release process, in which preformed interferon is rapidly released into the circulation by a process not requiring RNA or protein synthesis. 2- Nucleic Acids Double-stranded RNA molecules, either natural or synthetic, induce interferon formation in animals and tissue culture cells. There is some dispute about the mechanism involved, for although the process is sensitive to actinomycin, puromycin and p- fluorophenylanine, it is less sensitive than virus induced interferon formation. Nothing is yet known in molecular terms about the interaction between double-stranded RNA and the cell genome, although attempts to follow therr. autoradiographically are being made. It is now fàirly clear that single stranded RNA molecules can also induce interferon in tissue culture.