Neurotropic Cas-BR-E murine leukemia virus harbors several determinants of leukemogenicity mapping in different regions of the genome.
The infectious virus derived from the molecularly cloned genome of the neurotropic ecotropic murine Cas-BR-E retrovirus was previously shown to have retained the ability to induce hind-limb paralysis and leukemia when inoculated into susceptible mice (P. Jolicoeur, N. Nicolaiew, L. DesGroseillers, and E. Rassart, J. Virol. 45:1159-1163, 1983). To map the viral sequences encoding the leukemogenic determinant(s) of this virus, we used chimeric viral genomes constructed in vitro between cloned viral DNAs from the leukemogenic Cas-BR-E murine leukemia virus (MuLV) and from the related nonleukemogenic amphotropic 4070-A MuLV. Infectious chimeric MuLVs, recovered from NIH 3T3 cells microinjected with these DNAs, were inoculated into newborn NIH Swiss, SIM.S, and SWR/J mice to test their leukemogenic potential. We found that each chimeric MuLV, harboring either the long terminal repeat, the gag-pol, or the pol-env region of the Cas-BR-E MuLV genome, was leukemogenic, indicating that this virus harbors several determinants of leukemogenicity mapping in different regions of its genome. This result suggests that the amphotropic 4070-A MuLV has multiple regions along its genome which prevent the expression of its leukemogenic phenotype, and it also shows that substitution of only one of these regions for Cas-BR-E MuLV sequences is sufficient to make it leukemogenic.
D000818:Animals; D002678:Chimera; D002874:Chromosome Mapping; D005814:Genes, Viral; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000472:pathogenicity; D007942:Leukemia, Experimental / Q000235:genetics / Q000382:microbiology*; D051379:Mice; D008815:Mice, Inbred Strains; D010243:Paralysis / Q000382:microbiology; D012367:RNA, Viral / Q000235:genetics
D012367:RNA, Viral