Interferon induction by viruses: one molecule of dsRNA as the threshold for interferon induction. 1983

P I Marcus

The studies chronicled in this chapter were chosen largely because they contained data amenable to the quantitative analysis of interferon induction dose-response curves and the IFP activity they represented. The interpretation of the data was predicated on the assumption that a single molecule of dsRNA, when properly introduced into a cell, either as a preformed entity or formed therein following some synthetic event, can induce a quantum yield of interferon. This novel view of interferon induction by viruses has provided an explanation for many seemingly discordant results and offers a unifying hypothesis regarding the nature of the interferon inducer moiety for viruses from widely different families. If we note the reluctance of some to accept dsRNA as a common interferon inducer molecule ( McKimm and Rapp , 1977; Kowal and Youngner , 1978; Joklik , 1980) but recognize that the threshold for activating the interferon induction system is one molecule per cell, many aspects of interferon induction heretofore enigmatic are rendered offerpretable . Furthermore, one molecule of dsRNA per cell suffices to induce a quantum yield of interferon, an apparent expression of the "one-shot affair" of interferon production recognized by Ho (1964). In some cases of induction (the r = 1 type dose-response curve) there is an exquisitely responsive modulation of production when a second molecule of dsRNA is simultaneously introduced into the cell. The experimental approach and concepts discussed herein offer a new perspective on the mechanism of interferon induction by viruses and its regulation, and point out the incredible biological potency of a dsRNA molecule--a molecule found to play a key role in viral infection and host defence (Carter and De Clercq , 1974), regulation of the immune system (Johnson, 1980), and perhaps some yet to be defined function in cell growth (Taylor- Papadimitriou , 1980) and differentiation ( Grossberg and Sabran , 1981-2) through its capacity to activate the interferon system.

UI MeSH Term Description Entries
D007372 Interferons Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. Interferon
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002642 Chick Embryo The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching. Embryo, Chick,Chick Embryos,Embryos, Chick
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012330 RNA, Double-Stranded RNA consisting of two strands as opposed to the more prevalent single-stranded RNA. Most of the double-stranded segments are formed from transcription of DNA by intramolecular base-pairing of inverted complementary sequences separated by a single-stranded loop. Some double-stranded segments of RNA are normal in all organisms. Double-Stranded RNA,Double Stranded RNA,RNA, Double Stranded
D014780 Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Animal Viruses,Zoophaginae,Animal Virus,Virus,Virus, Animal,Viruses, Animal

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