Development and Regression of Shope Papillomas Induced in Newborn Domestic Rabbits

Abstract

Cutaneous papillomas induced in domestic rabbits by inoculation of Shope papilloma virus (SPV) are known to regress spontaneously in approximately 30-50% of infected animals (1, 2). The regression takes place 5 to 12 weeks after the inoculation of SPV and those animals in which the tumors fail to regress during this period tend to carry the tumors almost indefinitely. Considerable evidence indicates that the phenomenon of spontaneous regression is probably due to specific immunological reactions against the tumor (1, 3, 4). Although data have been presented showing that some serum factor interferes with the inhibitory ability of immune lymph-node cells against the tumor (9, further investigations are needed to elucidate why this regression is observed in some animals and not in others.We used newborn domestic rabbits to investigate possible immunological mechanisms responsible for the regression of Shope papillomas. Rabbits are born immunologically immature and gradually acquire immunological competence. Newborn animals were inoculated with SPV within the first 24 neonatal hr and were then kept under observation for more than 6 months. Development and regression of Shope papillomas in these animals were recorded and immunological analyses were performed. The findings are discussed in comparison with those in adult rabbits.Materials and Methods. Rabbits. Adult rabbits of both sexes were purchased from local dealers and newborn animals were obtained by mating these purchased animals. The newborn, within the first 24 neonatal hr, were inoculated intradermally at two sites on the dorsal area with 0.05 ml of SPV suspension.SPV. Glycerinated Shope papillomas were obtained from the Earl Johnson Farm, Rago, Kansas, and stored at -20" until use. 64Virus suspension was prepared as described previously (3) and a 10% suspension was used throughout the experiment.In vitro neutralization test of SPV. A 10% SPV suspension was mixed with an equal volume of serum specimen and allowed to react at 37" for 30-60 min. The mixture was examined for papilloma-inducing capacity by inoculation onto the skin of an adult rabbit by the scarification method (3). The virus suspension treated with normal rabbit serum was similarly inoculated into the same rabbit. The results were assessed 3 weeks after the inoculation according to the degree of the papilloma produced. No papilloma production was recorded as positive, reduced papilloma production compared with the control was taken as weakly positive, and papilloma production similar to that of the control was recorded as negative.Delayed-type hypersensitivity test with SPV. SPV was partially purified by two cycles of differential centrifugation at 10,OOOg for 10 min and at 40,OOOg for 1 hr. Protein concentration of the virus suspension, purified as such, was estimated to be 142.5 pg/ ml by the Lowry et al. modification of the Folin-Ciocalteu method, using a calibration curve of bovine serum albumin. The suspension (0.05 ml) was injected intradermally into the rabbits and the results were assess...

Seronegative virus carriers in the infection of rabbits with human T lymphotropic virus type I.

“…Glycerinated Shope papillomas were obtained from the Earl Johnson Farm (Rago, KS) and stored at -20°C until use . Virus suspension (10% tumor extract) was prepared as described previously (8) and 0 .05 ml of the suspension was injected intradermally on the dorsal area .…”

“…A 10% SPV suspension was mixed with an equal volume of serum specimen and allowed to react at 37°C for 30 min . The mixture was examined for papillomainducing capacity by inoculation onto the skin of an adult rabbit by the scarification method, as described previously (8) .…”

Immunopathology

“…In newborns the tumors progress and kill the host, whereas in adults the incidence of tumors is lower (McCoy et al, 1972) and they frequently regress, starting around day 13 (Fefer et al, 1967a,b). A similar situation holds true in the Shope fibroma and papilloma systems, where regression can be correlated with the development of delayed hypersensitivity to viral antigen and the inability of virus to multiply in infected tissues and in the RES (Allison, 1966;Seto et al, 1977;Sell and Scott, 1981).…”

Morphometric analysis and identification of infiltrating leucocytes in regressing and progressing shope rabbit papillomas

“…Tumors induced by the cottontail rabbit papillomavirus (CRPV) have long been studied as an animal model system for human papillomavirus infection (Evans et al, 1962;Kreider, 1963;Seto et al, 1977). In an ideal experiment, domestic rabbits are infected by cutaneous scarification with CRPV and, after a latency period of 2 to 3 weeks, papillomas appear at all inoculated sites.…”