Distinct helper virus requirements for Abelson murine leukemia virus-induced pre-B- and T-cell lymphomas.
Abelson murine leukemia virus (A-MuLV) can induce pre-B- or T-cell lymphomas (thymomas) in mice depending on the route and time of injection. Previous studies have shown that the choice of the helper virus used to rescue A-MuLV greatly influences its ability to induce pre-B-cell lymphomas. In this study, we investigated the role of the helper virus in A-MuLV-induced thymomas. A-MuLV rescued with the helper Moloney MuLV, BALB/c endogenous N-tropic MuLV, and two chimeric MuLVs derived from these two parents were injected intrathymically in young adult NIH Swiss mice. All four A-MuLV pseudotypes were found to be equally efficient in the induction of thymomas, whereas drastic differences were observed in their pre-B-cell lymphomagenic potential. Thymoma induction by A-MuLV was independent of the replication potential of the helper virus in the thymus, and no helper proviral sequences could be detected in the majority of thymomas induced by A-MuLV rescued with parental BALB/c endogenous or chimeric MuLVs. In the thymomas in which helper proviruses were present, none of them were found integrated in the Ahi-1 region, a common proviral integration site found in A-MuLV-induced pre-B-cell lymphomas (Y. Poirer, C. Kozak, and P. Jolicoeur, J. Virol. 62:3985-3992, 1988). In addition, helper-free stocks of A-MuLV were found to be as lymphomagneic as other pseudotypes in inducing thymomas after intrathymic inoculation, in contrast to their inability to induce pre-B-cell lymphomas when injected intraperitoneally in newborn mice. Restriction enzyme analysis revealed one to three A-MuLV proviruses in each thymoma, indicating the oligoclonality of these tumors. Analysis of the immunoglobulin and T-cell receptor loci confirmed that the major population of cells of these primary thymomas belongs to the T-cell lineage. Together, these results indicate that the helper virus has no effect in the induction of A-MuLV-induced T-cell lymphomas, in contrast to its important role in the induction of A-MuLV-induced pre-B-cell lymphomas. Our data also revealed distinct biological requirements for transformation of these two target cells by v-abl.
Poirier
Y
Y
Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Quebec, Canada.
Jolicoeur
P
P
D000011:Abelson murine leukemia virus / Q000235:genetics / Q000472:pathogenicity*; D000818:Animals; D001402:B-Lymphocytes; D015139:Blotting, Southern; D002472:Cell Transformation, Viral; D004273:DNA, Neoplasm / Q000235:genetics; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D006378:Helper Viruses / Q000235:genetics / Q000472:pathogenicity; D009052:Leukemia Virus, Murine / Q000472:pathogenicity*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000382:microbiology*; D051379:Mice; D009857:Oncogenes; D013601:T-Lymphocytes; D013945:Thymoma / Q000382:microbiology*; D014779:Virus Replication
D004273:DNA, Neoplasm