THE STRUCTURE OF VIRUSES 



127 



cleic acid in 0.4 31 borate buffer at pH 7.7 

 to be 0.10 square cm per day, which on the 

 basis of a spherical molecule would corre- 

 spond to a molecular weight of about 37,- 

 000. The manner in which the protein and 

 nucleic acid are combined in tobacco-mosaic 

 virus is not known. However, the fact 

 that the two are immediately split apart 

 on treatment with 5 per cent sodium hy- 

 droxide at 0° C, with 5 volumes of glacial 

 acetic acid, with 36 per cent urea in 0.1 

 M phosphate buffer at pH 8, or on heating 

 to 75° C, and that a fairly rapid disintegra- 

 tion occurs with 0.5 per cent dodecyl sul- 

 fate at pH 8 argues against the possibility 

 that they are combined through stable 

 chemical bonds. The fact that it has not 

 yet been found possible to secure evidence 

 for the dissociation of the two in the pres- 

 ence of various concentrations of salt, after 

 the manner in which sperm nucleoproteins 

 are dissociated, indicates that the linkage 

 is different and is probably somewhat 

 stronger than the usual salt bonds. It is 

 possible that the linkage is a very weak 

 ester or amide bond, or perhaps of the 

 hydrogen bond type that is being postu- 

 lated so freely at present in connection 

 with protein structure. Bernal and Fanku- 

 chen first deduced from X-ray data that 

 tobacco-mosaic virus contained equal sub- 

 units about 22 X 20 x20 A in size ; and on 

 the basis of X-ray work with nucleic acids, 

 Astbury has suggested that this sub-unit, 

 which would have a molecular weight of 

 about 7000, must consist of one nucleotide 

 combined with 54 amino acid residues. 

 However, Ross has calculated from data on 

 the amounts of some of the amino acids 

 which occur in small amounts that if the 

 virus is built up from similar repeat-units, 

 the minimum molecular weight of this sub- 

 unit must be of the order of 20,000 to 

 40,000. This value is in accord with Ber- 

 nal 's more recent estimate of 40,000 and 

 vtdth results obtained by means of the 

 analytical ultracentrifuge on alkali-dissoci- 

 ated virus and by means of osmotic pres- 

 sure and diffusion determinations on virus 

 dissociated in 36 per cent urea, all of which 

 indicated a molecular weight of the order 



of 50,000. It should be emphasized that 

 these sub-units cannot be regarded as vi- 

 rus, for they are not active. In the case 

 of alkali degradation, evidence was ob- 

 tained by means of the ultracentrifuge that 

 the virus is first broken down into large 

 inactive units, and these then continue to 

 break up until eventually the small units 

 are obtained. It has not been determined 

 whether or not the large units still contain 

 nucleic acid. It seems likely that a similar 

 gradual breakdown occurs in the degrada- 

 tion of virus in concentrated urea solution, 

 but it has not been demonstrated experi- 

 mentally as yet, although such studies 

 are in progress. The results indicate that 

 the virus activity is not due to a dissoci- 

 able prosthetic group, but rather to a 

 unique architecture that is characteristic 

 of the large molecule as a unit. Nucleic 

 acid appears to play an important role in 

 this structure, for it has been found in all 

 of the viruses that have been purified. 

 The nature of the combination appears to 

 vary somewhat, for it has already been 

 found that the nucleic acid is bound far 

 more strongly in latent mosaic than in to- 

 bacco mosaic virus. The elucidation of the 

 intimate structure which is characteristic 

 of viruses may appear hopeless in view of 

 the complexity and differences already 

 found. However, if they contain some- 

 what similar sub-units, a study of the vari- 

 ous degradation products should yield in- 

 formation concerning the general nature of 

 the sub-units, and although the elaboration 

 of their detailed structure may not be 

 achieved at an early date, it is possible 

 that the manner in which they are com- 

 bined to form the virus may be learned and 

 with this the secret of the activity. 



The fact that the addition of salts to solu- 

 tions of tobacco mosaic virus may cause the 

 nucleoprotein to come out of solution in the 

 form of long, thin, solid, needle-shaped 

 structures which are readily visible under 

 the microscope and which have been re- 

 garded as crystals, and that the material 

 could be crystallized repeatedly in a similar 

 manner have attracted much attention. It 

 should be noted, however, that crystalline 



