In 1957, while working on the mechanism of viral interference (specifically, the resistance of a cell infected with one virus to superinfection with a second unrelated virus) at the National Institute for Medical Research in London, Alick Isaacs (a British virologist) and Jean Lindenmann (a Swiss researcher) discovered interferons. As nonspecific antiviral agents, interferons inhibit intracellular viral replication and are synthesized by cells in response to viral infection.
The lack of virus specificity is explained by the fact that interferons do not react directly with the virion (the extracellular infective form of a virus) but rather put forth their protective effect by an intracellular mechanism. But with regard to the species of cells that produced them, interferons are specific. For example, interferons produced by human cells mainly protect human cells; they have little protective capacity for the cells of other animals.
Purified interferons from various sources consist of small proteins unusually stable at low pH (the measure of the acidity or basicity of a solution) and fairly resistant to heat. In the cold, for instance, these interferons resist a long exposure to pH 2. In another example, chick interferons lose half of their activity after 1 h at 70 degrees Celsius.
The mechanism of interferon induction by viruses appears to have a relation with the presence of double-stranded ribonucleic acids (RNAs) and certain synthetic polynucleotides with a high degree of helical conformation. On the other hand, double-stranded deoxyribonucleic acids (DNA) and DNA-RNA hybrids are relatively poor inducers.
Interferons cause antiviral resistance indirectly by inducing the synthesis of an antiviral protein by exposed cells. This means that protection by interferons is provided inevitably by an intracellular induction of host metabolism tending toward the subsequent synthesis of another set of molecules, the antiviral proteins. Inasmuch as what is involved here is an indirect inhibition of virus, it is not surprising that interferons are cell-specific rather than virus-specific.
The antiviral effect of interferons in preventing cell infection is only one of the aspects of interferon activity. The other facets include interferon effect on immune responses, on cell-membrane-related occurrences or conditions, and on cell-growth depression and modification. It is unfortunate that interferons are relatively unstable in tissue fluids. This means that interferon for antiviral therapy is not particularly useful clinically. Still, interferons may play a protective role during naturally acquired viral infections for the simple reason that they are produced more promptly than specific antibodies.
Sources:
1. “Interferon” by Dr. Margaret Hunt, on Microbiology and Immunology On-line, University of South Carolina School of Medicine.
2. “Nonspecific Defenses” by Ferdinando Dianzani and Samuel Baron, Medmicro Chapter 49 (online).
3. “Interferon”, on the Wikipedia.
