Studies on the modification, by various agents, of the heat sensitivity of poliovirus

Abstract

The decrease in heat sensitivity of Poliovirus, Type I, after incubation with cystine, has been studied. Characteristics of the inactivation by heat have also been studied. The results have led to an hypothesis which, while in no way completely satisfactory, provides a useful picture by which the data can be discussed, and also serves to indicate the areas to be clarified by future experiments. This hypothesis proposes the existence of two reactivity classes of viral sulfhydryl groups: -SH groups of the first class are oxidized by oxygen and by iodosobenzoic acid, probably to disulfides: -SH groups of the second class are so situated as to be unable to form disulfide bonds readily, and thus cannot be oxidized by oxygen, but can be oxidized to -SO2H or –SO3H by iodosobenzoic acid. The inactivation is postulated to consist of at least two steps: oxidation of sulfhydryl group(s), followed by denaturation of the viral protein. The existence of a denaturation step is suggested by the calculation of an Arrhenius constant for aerobic inactivation of 76,000 calories/mole. Evidence is presented to indicate that, at least in the case of oxidation by iodosobenzoate, the oxidation has a sensitizing effect; i.e., it increases the probability for the denaturation to occur. The main requirement for stabilization appears to be the formation of a disulfide bond between a half cystine molecule and the viral -SH group. No compound has been found to produce stabilization as complete as L-cystine. The results suggest that the other compounds tested do not react with the viral -SH groups, and therefore one cannot decide whether formation of disulfide bonds with a stabilizing compound is in itself sufficient for stabilization. This does indicate, however, that the -SH groups must occur in an extremely stereo-specific environment