WALKER 



inoculated mice are placed in a room at a temperature of 4 C, the 

 infection then becomes quite uniformly lethal. Figure 1 shows a 

 t)T)ical experiment. Acute, limited exposure to cold is not sufficient 

 to change this infection in adult mice from a restricted, asympto- 

 matic one into a fatal infection. Continued exposure through several 

 days is necessary (Fig. 2), 



That the deaths of inoculated mice at 4° C are related to viral 

 infection can be shown by neutralizing the virus with specific anti- 

 serum prior to injection or by passively immunizing the mice prior 

 to inoculation. This prevents the deaths at 4° C. In addition, it can 

 be shown that this phenomenon is not caused simply by inability of 

 mice with pancreatitis to survive in the cold, but is due to a real 

 enhancement of the infection. Measurementofvirus levels and study 

 of tissue histology indicate that at ordinary temperatures viral 

 multiplication is limited to the pancreas, but that in mice at 4 C, 

 viral multiplication and tissue damage takes place in many tissues. 

 Data on this point will be presented in a later section. 



An investigation of Briody and associates (Briody et al., 1953) 

 concerned with what could well be called inapparent infection is also 

 pertinent here. These workers examined the effect of cold on the 

 process of adaptation of influenza A' virus to multiplication in the 

 lungs of mice. Unadapted influenza virus usually multiplies to some 

 extent in mouse lungs, but it causes little pneumonia or mortality 

 until after a series of serial passages has resulted in a selection of 

 virus capable of rapid and abundant multiplication in the lungs of 

 mice. When inoculated mice were maintained at 5*^ C, however, the 

 virus grew to 100-fold higher levels, the extent of pneumonia was in- 

 creased and mice began to die of influenzal pneumonia after only a 

 few passages. 



Can Exposure to ColdSeriously Worsen an Apparent Viral Infection? 



This question, of course, is not very different from the previous 

 one, because in many instances the difference between inapparpit and 

 apparent infection is only one of degree. Nevertheless, ihe question 

 serves well to introduce work on myxoma virus infections. 



322 



