Erythroleukemia induction by replication-competent type C viruses cloned from the anemia- and polycythemia-inducing isolates of Friend leukemia virus.

Abstract

In this study, the biological properties of the replication-competent viruses, F-MuLVA, present in the anemia-inducing isolate of Friend leukemia virus complex (FV-A); and F-MuLVP, present in the polycythemia-inducing isolate of Friend leukemia virus complex (FV-P) have been examined. BALB/c mice infected as newborns with clonal isolates of F-MuLVA or F-MuLVP become anemic and show splenic enlargement characterized by an increased proportion of cells that resemble immature nucleated erythroid cells. In addition, the spleens of these F-MuLVA- or F-MuLVP-infected mice contain a markedly increased proportion of both erythropoietin-dependent erythroid progenitor cells and spectrin-containing erythroid cells. These results suggest that Friend murine leukemia virus (F-MuLV) by itself can induce an erythroleukemic transformation in newborn BALB/c mice similar to that induced by the anemia-inducing spleen focus-forming virus (SFFVA) in newborn or adult mice. Kinetic studies indicated that the alterations in hemopoietic cell populations induced by F-MuLVA or F-MuLVP in newborn BALB/c mice occurred more slowly than the rapid changes observed after infection with FV-A. In addition, adult BALB/c mice were fully susceptible to the erythroleukemic transformation induced by either SFFVA or SFFVP, whereas only newborn mice were susceptible to F-MuLV. Taken together, these results suggest that, although the replication-defective Friend spleen focus-forming viruses appear to be the major determinant of erythroleukemia induction in adults, the replication-competent helper F-MuLV also have erythroleukemic potential when assayed in newborn animals.

Modulation of erythropoiesis by the helper-independent Friend leukemia virus F-MuLV.

“…Based on the finding herein that a dramatic enhancement of BFU-E* was observed in these F-MuLV-infected spleens with no increase in the levels of the more mature CFU-E*, as in the case of the FV-A-and FV-P-infected mice (17)(18)(19)(20), it is tempting to postulate that the F-MuLV-transformed cells are less differentiated than those from the FV-A-or FV-P-infected spleens. Support of this hypothesis can also be found in the study of the recently established Friend erythroleukemic cell (FLC) lines from the F-MuLV-infected spleens (24,38).…”

“…On the basis of data reported previously (20,(23)(24)(25) and this communication, it is not possible to determine the target cell(s) for infection or transformation by F-MuLV, nor is it possible to determine the relative stage of differentiation of these F-MuLV-transformed cells with respect to those induced by the FV-A or FV-P complexes. Based on the finding herein that a dramatic enhancement of BFU-E* was observed in these F-MuLV-infected spleens with no increase in the levels of the more mature CFU-E*, as in the case of the FV-A-and FV-P-infected mice (17)(18)(19)(20), it is tempting to postulate that the F-MuLV-transformed cells are less differentiated than those from the FV-A-or FV-P-infected spleens.…”

“…Several reports (20,(23)(24)(25), however, indicate that when newborn BALB/c or NIH Swiss mice are used, the replication-independent F-MuLV, which has often been considered's simply the helper virus, can also induce splenomegaly. In this study, we examinedthe modulation of erythropoiesis by the replication-independent F-MuLV in newborn and adult mice.…”

Importance of Receptor Usage, Fli1 Activation, and Mouse Strain for the Stem Cell Specificity of 10A1 Murine Leukemia Virus Leukemogenicity

“…Notably, Fli1 was first identified as a common integration site in F-MuLV-induced erythroleukemia (with Ͼ80% correlation) (7,8,48) and has since been found to be a common integration site in "non-B/non-T-cell" tumors induced by Cas-Br-E and "myeloid leukemia" induced by Graffi-MuLV (9,13,41). A review of the literature and methodology used to classify these tumors suggests that they most likely represent the same disease entity, characterized by anemia, splenomegaly, and frequent infiltration of the liver but not lymph nodes (29,50,54,60). The target of transformation appears to be a very early progenitor, variably committed to the erythroid lineage (e.g., TER119 and/or cKit positive), probably explaining the discrepancies in the classification.…”

“…F-MuLV also uses the Cat1 receptor and induces an erythroleukemia, which strictly correlates with Fli1 integrations. A review of the literature describing the F-MuLV disease (29,50,54) suggested that 10A1-MuLV induces the same disease. It is known that F-MuLV does not induce an erythroleukemia in C57BL/6 mice.…”