RELATIONSHIP OF DONOR AGE TO IN VITRO PRODUCTION OF FOOT-AND-MOUTH DISEASE VIRUS BY MOUSE KIDNEY CELLS BY CHARLES H. CAMPBELL, tM.D. (From the Plum Island Animal Disease Laboratory, Animal Disease and Parasite

The development of age resistance by mice has been reported for a number of viral infections including infection wth foot-and-mouth disease virus (FMDV). Skinner (1) and Graves and Poppensiek (2) found that mice are rather uniformly susceptible to FMDV until they are approximately 2 weeks old, after which they progressively become resistant. At 5 to 6 weeks of age very few remain susceptible. Although age resistance has been demonstrated many times, the mechanism of this resistance is not clear (3). A number of possibilities have been investigated or suggested including blocking of virus pathways (4-7), production of inhibitory substances (8), production of more effective immunological responses with maturation (9, 10), and hormonal effects (11). There is also the possibility that age resistance is related to the production during maturation of cells resistant to virus infection. The studies of Goodman and Koprowski (12) and Kantoch et al. (13) on the association of cell susceptibility to susceptibility of cell donors provide evidence for this hypothesis. Previous to these investigations, Sabin and Olitsky (5) found a relation between intramuscular multiplication of vesicular stomatitis virus and age of the animal, and recently Lerner et al. (14) reported a similar relationship with Coxsackie A4 virus. Also working with Coxsackie viruses, Kunin (15) obtained evidence which indicated that the susceptibility of animals at various ages was related to the relative amount of receptor-like substances in the tissues. The experiments presented here were performed, therefore, to investigate the possibility of a cellular mechanism for the development of age resistance to FMDV. Kidney cells from mice 1 through 5 weeks of age were exposed to virus, and virus growth curves were obtained by assay of samples removed at various intervals. These growth curves were then compared to determine if a relationship existed between virus production and age of the cell donors.