INACTIVATION OP VIRUSES 395 



of mediating or facilitating the entrance of the virus particle into the host 

 cell. In those viruses (e.g., bacteriophage and myxoviruses) which possess a 

 highly specific receptor mechanism, the intact function of the receptor 

 mechanism seems to be an absolute condition for maintenance of infectivity. 

 EEE virus, in which similar although probably less specific mechanisms are 

 supposed to jDlay a part in infection, may apparently retain some infectivity, 

 even if these mechanisms are destroyed. In plant viruses, finally, capacity 

 of attachment to the cell surface is completely immaterial; apparently the 

 only mode by which infection can be achieved being a direct mechanical 

 introduction into the cytoplasm. The "reconstitution" phenomenon may 

 indicate, however, that the virus protein m TMV also serves some purpose 

 beyond that of a stabilizer in the extracellular phase.^ 



We no longer conceive of viruses as giant nucleoprotein molecules, but 

 recognize a structural organization of the particles, clearly on a supramo- 

 lecular level. As a consequence, we also have to assume a functional differ- 

 entiation withm the particle. We are not yet in a position to map out all the 

 details of the composite picture. It is obvious, however, that the infectivity 

 of a virus particle is not determined exclusively by the functional state of its 

 nucleic acid. These other properties (for the time being poorly understood) 

 which, together with the reproductive capacity, determine the infectivity will 

 be referred to as avidity of the virus. 



Present evidence indicates that an irreversible change in the nucleic acid 

 is sufficient to cause a complete loss of infectivity. Whether or not it is also 

 a necessary condition for inactivation is not equally clear. A chemical 

 alteration not involving the nucleic acid would, if the infectivity were affected 

 at aU, presumably lead only to a reduction in avidity which might, however, 

 well approach complete inertia. The more the virus is dependent upon 

 receptor mechanisms, the more easUy might such a situation become estab- 

 lished. In such cases the result of an infectivity test will depend largely upon 

 the conditions of the test, the type of host ceU used, the physiological condi- 

 tion of the ceE, the pH, the composition of the medium, etc. The tryptophan- 

 dependent bacteriophages might be mentioned as an illustration to the 

 general principle. More relevant, perhaps, is the observation by Miller and 

 Stanley (1942) that excessive substitution of amino and phenolic groupings 

 of TMV led to partial inactivation, the rate of which appeared to be much 

 higher when measured in Phaseolus vulgaris than when Nieotiana glutinosa 



^Spizizen (1957) recently published some interesting experiments on T2 bacterio- 

 phage, in which osmotic shock-inactivated virus was found infective for naked 

 protoplasts not only of the natural host strain but also of some under normal con- 

 ditions resistant strains of bacteria. In this case infectivity was destroyed by 

 proteolytic enzymes, whereas DNA ase seemed to have no specific effect upon the 

 virus. Pure nucleic acid prepared with Schramm's or Hart's techniques was not infective. 



