TEMPERATURE AND VIRAL INFECTION 



ants present a spectrum of viruses that are very closely related in 

 many physical and biological characteristics, including antigenic 

 makeup. However, after intradermal inoculation virulent myxoma 

 virus invades, causes generalizeddisease, and is almost 100 per cent 

 lethal for domestic rabbits, while fibroma virus causes only local 

 benign tumors that eventually regress without any apparent harm to 

 the rabbit. It is noteworthy that the only tissues in which fibroma 

 will multiply and cause lesions in the adult rabbit, even if injected 

 intraperitoneally or intravenously, are the surface tissues of skin 

 and testes. It can be demonstrated quite easily that myxoma and 

 fibroma viruses differ markedly in their capacity to multiply at 

 temperatures above 35° C. Thompson (1938) demonstrated this in 

 vivo when he raised the skin temperature of rabbits by exposure to 

 heat and showed that fibroma lesions were quite easily inhibited 

 while the disease caused by virulent myxoma virus required higher 

 temperatures to bring about amelioration. This can be shown in 

 primary cultures of rabbit tissues in vitro. Kilham (1959) has pro- 

 vided some data onthis,andsomeof our own data are shown in Fig- 

 ure 7. Fully virulent myxoma virus multiplies to high titer even at 

 temperatures of 40° C to 41 C, while fibroma virus reaches peak 

 titers at 32° C to 35° C and is inhibited to some extent at tempera- 

 tures as low as 36° C to 37° C and is severly inhibited at higher 

 temperatures. Variants of myxoma virus exist that are reduced in 

 their virulence and are intermediate between myxoma and fibroma 

 viruses in the characteristics of the disease that they produce in 

 rabbits. It was one of these that Marshall used in his study. We are 

 currently comparing the capacity of myxoma virus strains to multi- 

 ply at various temperatures and their relative invasiveness and viru- 

 lence in rabbits.This work has not progressed far, but it appears that 

 for many attenuated strains reduction in virulence is accompanied by 

 decreased capacity to multiply at temperatures comparable to the 

 internal temperature of the rabbit. 



Other studies indicating a relationship between virulence and 

 capacity to multiply at temperatures above 37° C can be cited. Bed- 

 son and Dumbell (1961) have shown this relationship with several 

 poxviruses and their virulence for chicken embryos. Most detailed, 

 however, have been the extensive studies of Lwoff and associates on 

 poliovirus (Lwoff, 1959; Lwoff and Lwoff, 1960, 1961). Lwoff has 

 demonstrated in cells in culture that poliovirus is able to multiply 



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