THERMAL INACTIVATION OF VIRUSES 119 



content of the broth used, it is quite possible that the effect of 

 pressure is to cause a change in AF* such that different parts of 

 the virus, with normally slower rate constants, become the rate 

 determining factor. It must never be lost sight of, in this kind 

 of work, that a virus is not a single molecule but, at best, a 

 molecular aggregation. 



A rather different approach from the statistical-thermo- 

 dynamical reasoning of the Eyring theory may be more signif- 

 icant. It seems very likely that the nucleoproteins of viruses 

 have very high changes in volume under pressure. This means 

 that a fair fraction of the bonds are capable of changing their 

 average spacing. If the energy of binding of such bonds is 

 strongly distance dependent, the increased proximity of the 

 bound groupings may increase the stability of the molecule as 

 regards thermal agitation. The ])ositive AV^, which means that 

 the molecule must expand to inactivate, is thus to be linked with 

 the idea that the molecule with high AV^ contains bonds which 

 are quite distance de])endent. 



Since the above measurements were made on infectivity, 

 which perhaps is related to nucleoprotein, a completely different 

 set of values would be expected for change in serological affinity, 

 which is related to the surface protein. Studies which could be 

 used to measure AV^ for such treatment have not yet been made. 



Conclusions from Thermal-Inactivation Studies 



Virus inactivation seems to follow first-order reaction kinetics 

 with an energy of activation in the dry state of around 1 ev. 

 The constants in the wet state indicate that higher energy 

 barriers have to be overcome, so that tighter binding of the whole 

 structure holds in the wet state. This is at the expense of a high, 

 positive entropy of activation, corresponding to the binding 

 of considerable water, with consequent reduction in possible 

 degrees of freedom, and renders the virus quite susceptible to 

 inactivation if the temperatures are high enough. Thus, viruses 

 seem to be stable when dry if the drying process can be con- 

 ducted so as to retain the virus structure intact, but the tempera- 

 ture must be kept low in many cases or the virus slowly gets 



