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

Abstract

Friend leukemia virus (FLV) is a complex of two viruses, a defective spleen focus-forming component (SFFV) and a helper-independent virus, F-MuLV. Although the effects of the erythropoietic changes in susceptible adult mice after infection of FLV have been attributed to the SFFV component, it has been shown that the F-MuLV alone can induce certain erythropoietic changes in susceptible newborn mice. In the present study, we have shown that very different erythropoietic changes were observed after infection with F-MuLV. Unlike the FLV complexes, the F-MuLV did not induce in newborn BALB/c mice an increase in the erythroid progenitor cells (CFU-E*). Instead, a dramatic increase in the bursts (BFU-E*) can be detected in the infected spleens and marrows. The frequency of BFU-E* in the infected spleens increased to a level of ~1,500/105 cells or 5 x 107/spleen. In the marrows, frequency increased to a level of 300 BFU-E*/105 cells or ~3 x 105/femur. These F-MuLV-induced bursts, BFU-E*, differ from the BFU-E in uninfected mice. For example, although the morphology of the erythroid bursts in the F-MuLV infected mice was similar to that in the uninfected mice, the colonies were less hemoglobinized when compared with those in the uninfected mice. We have also shown that if adult BALB/c or DBA/2 mice were administered phenylhydrazine (PHZ), infection of cloned F-MuLV can induce certain erythropoietic changes. For example, although F-MuLV alone had little effect on the spleen weights (0.1-0.15 g) of adult mice and PHZ can only moderately increase the spleen weights (0.3 g), infection of F-MuLV in PHZ-treated mice can induce a severe splenomegaly (~1 g). Similarly, the infection of F-MuLV in PHZ-treated mice can also induce a severe anemia and an increase in the frequency of CFU-E*. These results indicate that F-MuLV, without the SFFV components, can modulate erythropoesis in newborn and adult mice. The finding that F-MuLV in newborn BALB/c mice elicit very different erythropoietic changes also has interesting implications. The induction of a dramatic increase in BFU-E* with no increase (possibly even a slight decrease) in CFU-E* implies that the leukemic block in F-MuLV-infected newborn mice is at a stage between BFU-E and CFU-E. The data also suggest that F-MuLV infect different, possibly more immature, erythroid target cells than the FLV complexes.