98 Essays in Biochemistry 



studied in the hope that it will reveal something of the in vivo process 

 of invasion. 



Under normal physiological conditions, the irreversible phase of 

 adsorption is followed by a splitting of the coliphage particle, so that 

 the bulk of the nucleic acid of the phage particle passes into the 

 bacterial cell. The protein membrane remains attached to the exterior 

 of the cell and can be removed, without interfering with the further 

 stages of virus reproduction, simply by agitating the infected bacterial 

 cells in a Waring Blendor. All or almost all the phage DNA is trans- 

 ferred into the bacterial cell, and probably all the phage protein is 

 excluded. The further steps in the process of virus synthesis involve 

 the participation of only a portion of the original infecting particle, 

 that is, the whole or the major part of its nucleic acid. This, however, 

 does not deny the physiological importance of the protein portion of 

 the viral particle. The antigenic properties of the virus reside entirely 

 in the protein coat. Further, since protein ghosts, free of nucleic acid, 

 are capable of being adsorbed to and of killing bacterial cells, the 

 protein portion of the phage is capable of initiating some type of 

 intracellular reaction. Finally, no one has yet succeeded in inducing 

 the infectious process by protein-free nucleic acid preparations. It is 

 not possible to conclude that the role of the viral protein is simply 

 that of introducing the DNA into the host cell, but certainly its effect 

 must be exerted in the early stages of invasion. 



The nature of the forces responsible for the "injection" of the viral 

 nucleic acid into the bacterial cell is entirely obscure. It has been 

 suggested that the adsorption process involves the splitting off of a 

 portion of the bacterial membrane, that the virus-host cell system 

 can be considered as a single system, and that ordinary osmotic forces 

 would be sufficient to explain the passage of the viral DNA from the 

 head of the viral particle into the bacterial cell proper. 



In any event, it is not possible to detect the presence of intact virus 

 during the next phase of viral reproduction. If the cells are disrupted 

 during this period, one finds particles which are protein in nature, 

 related serologically to virus protein, but incapable of inducing the 

 virus infection, and representing probably intermediate stages in virus 

 synthesis. Since the DNA of T 2 , T 4 , and T, ; contains 5-HMC and is 

 free of cytosine, one can study the synthesis of the nucleic acid portion 

 of the virus by following the changes in phage-specific DNA (i.e., DNA 

 containing 5-HMC) and of host-specific DNA (containing cytosine 

 and no 5-HMC) at intervals after infection has occurred. Phage DNA 

 is found to increase soon after infection, while the bacterial DNA 



