Veterinary and Biomedical Sciences, Department of


Date of this Version



Annual Review of Microbiology 18 (1964), pp 269-300


There is a strong tendency in current research on mammalian virus diseases to concentrate on virus activity at a cellular or subcellular level. This trend is summarized adequately by Enders in relation to viral replication as follows: ','The large and ever-increasing volume of published experimental work on viral replication strikingly reveals the central position of this phenomenon in contemporary virological research. There are good reasons, both biological and practical, underlying this intensive effort to understand, i n detail, how a virus particle, without energy transforming apparatus of its own, manages to utilize the metabolic equipment of the cell to produce itself. At present, the specialists in this subject conceive of replication as mediated essentially by viral nucleic acids which assume the role of the cellular n ucleic acids, thereby directing the synthesis of more nucleic acid of their own kind and providing the information necessary for the manufacture of more viral protein . The enzymatic complement for these syntheses is supplied by the host cell, and the metabolic sequences are not considered to differ in essence from those involved in the manufacture of cellular nucleic acids and proteins." Unquestionably, basic research directed toward an understanding of virus replication will play an important role in the eventual control of virus infections whether in man or his animals. Viruses in tissue culture systems may behave quite differently than in the' total animal host. Essentially, there are no restraining influences so that viruses 'may replicate in culture at will with severe damage to or destruction of the cells they attack. A parallel seemingly exists between virus replication in a tissue culture system and replication in the total host with the experimental production of clinical or subclinical disease. The virus which causes infectious bovine rhinotracheitis of cattle behaves in this manner. However, the virus which attacks a tissue culture system with all the traits of a pathogenic entity, including. cytopathogenic effects on cells, yet lacks the capacity to cause measureable disease in the fully susceptible host, does not fit the model. Beran's swine enterovirus behaves in this' manner. More difficult to explain is the virus that [causes] disease and death in a specific host yet resists adaptation to tissue culture systems, in spite 'of every device the investigator may employ to. encourage adaptation . ' This category is 'fulfilled by transmissible gastroenteritis virus of swine. All three viruses will be discussed later in ·this chapter . . Although.much.can be learned about viruses and virus infections in relatively simple systems, diseases in. the animal and their control are still of paramount importance. Contemporary virological research, then, must maintain a proportionate balance 'between studies at the cellular and subcellular levels and those conducted within the animal host. Use of health-defined animals in experimental programs in recent years has greatly strengthened the position of those who would attempt to gain understanding of disease processes in the animal.