Low‐leukemogenic variants of rauscher leukemia virus obtained in long‐term cultures at supra‐optimal temperature

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Abstract
Taking as a starting point the previously demonstrated genetic variability of in vitro cultivated murine leukemia viruses (MuLV), with particular regard to their leukemogenic potential, an attempt was made to accumulate and study Rauscher leukemia virus (RLV) variants selected by long‐term cultivation at a supra‐optimal temperature of 40.5°C (± 0.5°C). The most significant results were obtained with cells of the CL91 line originating from normal C57BL lung tissue, initially virus‐free and infected with a highly leukemogenic RLV prepared from leukemic spleens. After 184 days of cultivation, the infected cells were divided into two parallel series: (I) the CL91RR which was continued at 37°C, (2) the CL91RRHT series which was transferred, after a transitory adaptation period at 39°C, for permanent culture at 40.5°C. Supernatants from the parallel series were checked periodically for their leukemogenic capacity as related to the number of virions found in the supernatant aliquots inoculated into sensitive weanling or new‐born BALB/c mice. The number of virions present in the CL91RRHT supernatants was regularly at least equal but usually significantly higher than in parallel CL91RR cultures. However, the leukemia‐producing capacity of the first was very low: only 11% of leukemias were obtained after an average of 98 days' latency with the CL91RRHT supernatants, when checked after 201 or more days of culture at 40.5°C, as compared with an average of 89% rapidly evolving leukemias (within an average of 23 days) obtained with material from CL91RR cultures. These differences were seen repeatedly in 19 independent assays performed on a total of 132 and 111 animals, respectively, and extending over an experimental period of 586 days following the in vitro infection. These results were discussed in the light of other data concerning temperature‐dependent selection of variants of pathogenic viruses.