564 S. E. LURIA 



the replication of tlie genetic material, a clearly antocatalytic process, and 

 the maturation of new virus, in which the genetic elements stop replicating 

 and become assembled mto virus particles, by joining up with materials 

 synthesized under the heterocatalytic control of the virus. Cell- specific 

 materials, either genetically competent (as in transduction) or presumably 

 with structural functions (as in influenza viruses), may also become included 

 into virus particles. In its functional state within a cell, the genetic material 

 of a virus can control, not only the synthesis and assembly of constituents 

 of the mature virus particles, but also the production of essential enzymatic 

 mechanisms and other biochemical processes, which manifest themselves as 

 altered cell functions. Some of these functions of a virus may be instances of 

 pleiotropic gene action, by which genetic functions essential for virus multi- 

 plication accidentally affect other cell functions. It is equally conceivable, 

 however, that a virus, as a transmissible fragment of cell heredity, may con- 

 tain the genetic determinants of functions unrelated to its own perpetuation 

 as virus. 



A number of questions may now be raised: How does virus multiplication 

 lead to the cellular dysfunctions observed in many viral infections? Which 

 cellular properties are determmed by genetic elements that can act as viruses? 

 And what relationship exists between these elements and the other genetic 

 elements of the cell? 



B. Cell Damage and Virus Multiplication 



Cellular dysfimction may result from any of the phases of interaction 

 between viruses and cells. With certain "intemperate" phages, for example, 

 the mere attachment of a virus particle, even unable to multiply, can cause 

 irreparable damage and ceU death. Other changes in cell properties, Hke the 

 antigenic changes in phage-uifected bacteria, are observed whenever viral 

 multiplication occurs, either in the vegetative or the prophage state. Still 

 other forms of damage, such as lysis of bacteria by phage or destruction of 

 animal cells by certain viruses, are probably tied up with the process of virus 

 maturation. 



Replication of a virus in a noninfectious form, either as vegetative virus 

 or as provirus, is often compatible with continued cell life and cell division, 

 as in lysogenic bacteria. Virus maturation, which involves extensive 

 changes in the pattern of cellular biosynthesis, is probably more directly 

 related to cellular damage leading to cell death. Even in some prolifer- 

 ative virus diseases the mature, infectious virus particles might be pro- 

 duced only in a few cells that are prevented from further growth. At least 

 for Rous sarcoma, however, there is now some evidence of production of 

 mature virus by living, multiplying cells (Rubin and Temin, 1959). 



