53 VIRUSES AS ORGAfTISUS 



A third line of evidence can "be brought to bear on the choice between the 

 two alternative theories. If the leaf of a plant such as Nicotiana glutinosa 

 is rubbed with a mixture of two viruses, for example, ordinary tobacco mosaic 

 virus and the acuba mosaic strain of tobacco mosaic virus, one might expect that 

 if infection is due to a single virus particle, the local lesions produced on 

 this leaf ought to contain, for the most part, only one virus, either ordinary 

 tobacco mosaic virus or the acuba strain. In fact one can calculate from the 

 theory that virus infection is the result of at least one particle favorably 

 situated, the proportion of lesions which should contain both viruses and the 

 proportion which should contain either the one or the other. I'he reason that 

 some lesions should contain both viruses is simple, for the theory states that 

 a lesion is the result of one or more particles being favorably situated. One 

 particle is sufficient, but when the virus concentration is high enough more 

 than one particle is apt to be present. Under such circumstances infection 

 could be the result of several particles acting simultaneously. Jfrom the simple 

 probability theory, one obtains the result that when the dose of mixed virus ap- 

 plied is very concentrated, a high percentage of the local lesions should be 

 mixtures, but when the concentration of the mixture applied 1b bo low that only 

 an occasional lesion is produced, the percentage of mixed Infections should be 

 extremely low - less than 1/8. Similarly, it is possible to determine the per- 

 centage of mixed infections that should be expected if the host variation theory 

 is correct. According to this theory, the host has a defense mechanism which is 

 capable of overpowering a certain number of virus particles, but which will be 

 itself overpowered by a greater number. Suppose, for example, that the defense 

 mechanism of some particular host cell is capable of overpowering exactly 1000 

 virus units. If 1000 units of mixedivirus are applied to this particular host, 

 no lesion will result. If 1001 units are applied, a lesion will result, and 

 this lesion will be either tobacco mosaic virus or acuba mosaic. If 1002 units 

 are applied, there will be two virus units left over to cause am infection, and 

 the chances are fairly good that the resultant infection will be mixed, that is, 

 contain both viruses. If 1010 units are applied, there will be 10 left over, 

 and, under these circumstances, it is virtually certain that the lesion would 

 be compound. It is evident that the concentration range between the point at 

 which one obtains no lesions and the point at which one is almost certain to ob- 

 tain mixed Infection is only 1%. Thus, it is virtually certain that a lesion 

 will be compound, if host response to dosage level is due to variation in host 

 susceptibility. This is true even for relatively low concentrations of inocu- 

 lating medium. 



An actual experiment was carried out in which a mixture of acuba and to- 

 bacco mosaic viruses was spread over the leaves of Nlcotiana langsdoril plants. 

 Necrotic local lesions were obtained. These lesions were then punched out from 

 the leaf, ground up, and inoculated onto Nlcotiana sylvestris plants. This 

 plant gives local lesions with acuba mosaic virus but systemic infections with 

 tobacco mosaic virus. Thus, it can be used as an indicator to tell which virus 

 is present in the lesion from the langsdoril plant. In this study it is found 

 that when the concentration of the mixed Inocula was very low, the proportion 

 of mixed infections was very low. This result is consistent with the assumption 

 that Infection can be initiated by a single particle favorably located, but it 

 is totally inconsistent with the assumption that dose response is an expresalon 

 of variation of host susceptibility. 



Thus, three lines of evidence have been brought to bear upon the question 

 of deciding between the two theories of virus infectlvity. All three indicate 

 that the theory that dose response is an expression of variability in host 

 susceptibility is untenable. Therefore this theory can be eliminated. The only 

 theory that remains is that virus Infection is the result of at least one virus 

 particle being present in a favorable location. The fact that the data at pres- 

 ent available agree with this theory does not of course prove that this mechanism 

 is correct. It merely permits the conclusion that it is the only mechanism yet 

 thought up which can be supported by the data at present available. On the basis 

 of present knowledge, therefore, the proposition that one infectious unit can 



