INTRACELLULAR MULTIPLICATION OF BACTERIAL VIRUSES 271 



Incomplete forms of phage proteins have also been detected in bacteria 

 infected with phage types outside the T-even series. For instance, complement- 

 fixing phage antigens are present in phage 3A-infected staphylococci and T5- 

 infected coli in advance of the appearance of any mature progeny, and the 

 total compliment-fixing activity present at later times of the latent period is 

 always in excess of that accounted for by infective phage particles (Romitree, 

 1951, 1952; Lanni, 1954). In the case of T3 phage, however, no neutralizing 

 antigens seem to be present in the infected cells either in advance of the 

 appearance of infective progeny or in excess of that accounted for by the 

 mature progeny (Barry, 1954). Empty phage heads, like the T-even dough- 

 nuts, have been observed in electron micrographs of lysed coH in which 

 development of phage A is mider way (Kellenberger and Kellenberger, 1957). 

 Also, proflavine interferes with the maturation of phages Tl, T3, T5, and T7 

 in a manner similar to its inhibitory effects on the T-even group (Foster, 1948). 

 Indeed, in the case of some temperate j9yoc?/anea, megatherium, and coHphages, 

 the effect of proflavine of preventing the maturation of complete phage 

 particles can also be produced by a genetic alteration of the prophage of a 

 lysogenic bacterium. In such "defective" lysogenic strains, phage develop- 

 ment can be induced by the usual means (cf. Chap. 9). After a time correspond- 

 ing to the normal latent period, the defective lysogenic cells lyse and liberate 

 both the genetic material and the protein of the progeny, without yielding 

 any morphologically intact, infective phage particles (Jacob, 1950; Lwoff and 

 Siminovitch, 1951; Lederberg and Lederberg, 1953; Appleyard, 1954; Jacob 

 and Wollman, 1956). Finally, also, phenotypic mixing does not appear to be 

 restricted to the T-even phages, since it has been observed with Tl (Tessman 

 and Ozaki, 1957) and with A (Appleyard et al., 1956). It appears, therefore, 

 that the notion of spatially separate synthesis of phage nucleic acid and 

 phage protein can be extended with some justification to bacterial viruses 

 other than the T-even group. Unfortunately, however, there is no immediate 

 prospect of studying the intracellular appearance of phage DNA of any strains 

 other than the T-even, or carrying out chemical "pool-size" measurements of 

 phage precursor nucleic acid, since thus far only the DNA of the T-even 

 phages is known to be sufiiciently different in composition from the DNA of 

 their host, so that phage DNA can be recognized specifically in the presence 

 of host DNA (Cohen, 1955). For this same reason, it has not yet been possible 

 to ascertain whether or not the fact that protein Sjmthesis inhibitors, such as 

 chloramphenicol, arrest the intracellular multiplication of Tl and A bacterio- 

 phages (Bozeman et al., 1954; Miki and Matsushita, 1956) means that the 

 synthesis of the DNA of these strains also cannot get underway miless the 

 formation of a "nonprecursor" protein is first allowed to take place. (A report 

 that DNA S5^lthesis does proceed in bacteria which have been infected in the 

 presence of chloramphenicol with any one of a number of phage strains other 



