276 HEINZ SCHUSTER 



RNA, have an inhibitory action on virus multiplication due to their anti- 

 metabolic activity. Several of these compounds have been investigated in 

 detail with respect to their action on the multiplication of TMV. These are 

 8-azaguanine, 2-thiouracil, and 5-nuorouracil. 5-Bromouracil, which is in- 

 corporated into phage DNA in place of thymine and which greatly reduces 

 the infectivity of phage particles, 105 has no action on TMV. An excellent 

 summary of the studies on purine and pyrimidine analogs has recently been 

 published. 106 



Azaguanine. Azaguanine will inhibit virus multiplication in tobacco 

 leaves infected with TMV. 106 This inhibition can be abolished if plants are 

 treated, at the same time, with several naturally-occurring purines, their 

 ribosides or ribonucleotides. RNA extracted from TMV, grown in leaves 

 in the presence of azaguanine, contains about 3 % less guanine than RNA 

 from normal virus. An alkaline hydrolysis of the RNA obtained from 

 "azaguanine-TMV" shows that the compound has been incorporated into 

 the RNA as a nucleotide. 107 The presence of azaguanine in RNA can be 

 demonstrated without great difficulty because azaguanine fluoresces 

 strongly under both acid and alkaline conditions, while guanine compounds 

 fluoresce strongly only under acid conditions. 8-Azaguanylic acid may be 

 demonstrated by paper electrophoresis of the alkaline digest. 



TMV preparations, having azaguanine in the RNA, are of lower infec- 

 tivity than an equivalent amount of normal TMV. 108 Similar observations 

 have been made with turnip yellow mosaic virus. In the latter case, the 

 ratio of azaguanylic acid to guanylic acid could not be determined because 

 the amount of azaguanine incorporated into the nucleic acid was too 

 small. 109 The decrease in specific infectivity is dependent on the length of 

 the time of multiplication of virus in the host cell in the presence of aza- 

 guanine. For example, virus particles, from 3 day-old infections, in treated 

 plants show a reduction in infectivity, whereas no difference in infectivity 

 could be detected in material from 14 day-old TMV infections of control 

 and azaguanine treated plants. The reasons for this behavior are not yet 

 clear. 



2-Thiouracil. Thiouracil can also be incorporated into TMV if infected 

 tobacco leaves are incubated in a medium containing this compound. 110 

 Virus multiplication is inhibited in the presence of thiouracil more effec- 

 tively than by azaguanine. 111 The incorporation of thiouracil into TMV 



105 D. B. Dunn and J. B. Smith, Nature 174, 305 (1954). 



106 R. E. F. Matthews and J. D. Smith, Advances in Virus Research 3, 49 (1955). 



107 R. E. F. Matthews, Nature 171, 1065 (1953). 



108 R. E. F. Matthews, J. Gen. Microbiol. 10, 521 (1954). 



109 R. E. F. Matthews, Virology 1, 165 (1955). 



110 R. Jeener and J. Rosseels, Biochim. et Biophys. Acta 11, 438 (1953). 



111 F. L. Mercer, T. E. Lindhorst, and B. Commoner, Science 117, 558 (1953). 



