INACTIVATION OF VIRUSES 403 



regular first-order reaction. On this condition the results reported by Lycke 

 (1958) indicated an energy of activation of about 20,000 cal./mole; the 

 reaction rate showed a minimum at pH about 7, increasing at more acid as 

 well as more alkaline reactions, 



6. Foot-and-Mouth Disease Virus 



Kinetic studies were recently reported by Bachrach et al. (1957) and by 

 Wesslen and Dmter (1957). The latter authors observed inactivation curves 

 of the same type as those obtained with poliovirus. 



7. General Remarks 



As previously pointed out, the relative importance of reactions m the 

 nucleic acid and the non-nucleic acid components, respectively, might be 

 expected to vary from one virus to the next, depending on the extent to 

 which receptor mechanisms play essential parts in infection. To aU appear- 

 ances, however, the activity of receptor groups of bacteriophage and myxo- 

 viruses is largely unaffected by treatment with formaldehyde in concentra- 

 tions and for periods of time sufficient to cause practically complete loss of 

 infectivity. Therefore, destruction of the reproductive capacity seems to be 

 the prmcipal mechanism in formaldehyde inactivation of all viruses. The 

 kinetics of inactivation should thus be determined mainly by the accessi- 

 bihty of the nucleic acid, the composition and structure of the protective 

 cover, and the type of interaction between the latter and the chemical agent. 

 Under such conditions lipid-containing and lipid-free viruses might be ex- 

 pected to show some distinctive features. This problem has not yet been 

 systematically studied. A priori, the "membrane effect" seems likely to be 

 the decisive factor, any possible differences being by degree rather than in 

 principle. As a matter of fact, in this writer's laboratory the polioviruses, 

 TheUer's virus, influenza A virus, and a staphylococcus phage were a]] found 

 to follow the pattern formulated in equation (1), which also fits Ross and 

 Stanley's data on TMV, as well as Wesslen and Dinter's on foot-and-moutli 

 virus. 



Theoretically, formaldehyde might be expected to penetrate the protein 

 coat either by diffusion or stepwise in a series of reversible reactions. The 

 observation by Cartwright et al. (1956) that preparatory substitution of SH 

 or NH2 groups does not demonstrably affect the initial rate of inactivation 

 of TMV speaks decidedly in favor of diffusion as the more important factor. 

 Whichever is the case, the progressive "fixation" or tanning of the protem in 

 the course of formaldehyde treatment will lower its permeability. Thus, a 

 membrane effect is to be expected, manifesting itself in a gradual decrease 

 in the rate of inactivation. The problem can be treated mathematically after 

 the followuig simplifying assumptions: (a) the fixation of the protein is 



