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CHAPTER III 



DISINTEGRATION OP VIRUSES 

 Introduction 



Virologists and bacteriologists have long recognized that some viruses and 

 also some bacteria are much more stable to heat than others. In fact, the ther- 

 mal death point has come to be recognized as one of the importauit characteristics 

 of such agents. It was thought, at one time, that the thermal death point was a 

 specific temperature below which the virus was stable and above which it became 

 Inactivated or killed. However, in more recent years, biologists have come to 

 realize that in reality no such thing as a thermal death point exists. The in- 

 activation of a virus is now recognized as a process which goes on at all tem- 

 peratures but which, like most chemical reactions, proceeds more rapidly at high 

 temperatures than at low temperatures. In view of this concept, the thermal 

 death point, or the thermal inactivation point, merely becomes that temperature 

 at which the rate of inactivation is sufficiently high so that most of the activ- 

 ity is destroyed during the arbitrary period of time chosen for the experiment. 

 It is evident, under these circumstances, that the concept of a thermal death 

 point or thermal inactivation temperature is not as useful as specific knowledge 

 concerning the way in which inactivation rate varies with the temperature. The 

 question of thermal stability of viimses is thus reduced to a problem in kinet- 

 ics. It has been shown through many studies that the destruction of biological 

 activity can be thought of as being one phase of the more general problem of de- 

 naturatlon of proteins. In view of this background, it was thought worthwhile 

 to investigate not only the inactivation but also the disintegration or denatur- 

 atlon of virus proteins. Tobacco mosaic virus and influenza virus have been 

 studied in greatest detail. The remainder of this chapter will consist of an 

 examination of some of the results obtained in these studies. 



Tobacco Itosalc Virus 



It has been known for several years that the ability of tobacco mosaic 

 virus to infect plants could be destroyed by heating at rather high temperatures, 

 between 90° and 100° C. After tobacco mosaic virus was isolated and purified by 

 Stanley, it became possible to study the denaturation of tobacco mosaic virus 

 protein at high temperatures. The unfortunately sunblguous terra, denaturation, 

 will be defined for the purpose of the present discussion, as the changes that 

 take place when a protein capable of being dissolved in neutral salt solutions 

 is transformed into a state in which it is no longer soluble in such solvents. 

 When a neutral solution of tobacco mosaic virus is heated to 80" or 90" 0., 

 virus infectivity is lost and a curdy precipitate forms gradually and does not 

 redlssolve upon cooling. This insoluable material has a molecular weight, not 

 of thirty million, but of less than one. hundred thousand. The kinetics of the 

 denaturation of tobacco mosaic virus was studied in cooperation with Price at the 

 Rockefeller Institute. This was done by measuring chemically the amount of to- 

 bacco mosaic virus remaining in solution after various periods of heating at 

 known temperatures. The results of a typical experiment are shown in Figure 25» 



