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

Abstract

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.