Until 1963, only viruses were known to stimulate interferon production in cells. The nucleic acid of the virus was generally regarded as the essential stimulus for interferon production.1 Rotem et al and Isaacs et al2,3 demonstrated in 1963 that nonviral nucleic acids, provided they were foreign to the cells (heterologous or chemically modified homologous RNA), could also initiate the production of interferon. Although their "foreign nucleic acid" hypothesis was received with some scepticism and retracted later,4 it offered a reasonable explanation for the nucleic acid-induced resistance to viral infection, which had been described5 as early as 1953. Moreover, it raised a possible explanation for the antiviral action of agents such as bacteria or apparently nonviral agents as the mold products statolon (culture filtrate of Penicillium stoloniferum) and helenine (mycelium extract of Penicillium funiculosum) which had been found active in a number of experimental viral infections.6-13
De Clercq E, Merigan TC. Induction of Interferon by Nonviral Agents. Arch Intern Med. 1970;126(1):94–108. doi:10.1001/archinte.1970.00310070096009
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