Isolation of transplantable erythroleukemia cells from mice infected with helper-independent Friend murine leukemia virus

Abstract

The Friend virus complex contains a helper-independent retrovirus, F- MuLV, and a replication-defective retrovirus, SFFV. Murine erythroleukemia cell lines (MEL) have been isolated previously from the leukemic tissues of mice infected with such stocks of Friend virus complex. Since our laboratory has shown that either F-MuLV or SFFV can induce a lethal erythroproliferative disease, it has been unclear which of the properties of conventional MEL cells were causally related to the infection of these cells by F-MuLV and which properties were related to the infection of these cells by SFFV. In this article, we have focused on the helper-independent component of the Friend virus complex, F-MuLV clone 57, which has recently been purified by molecular cloning. We report a method for the reproducible isolation of a new type of murine erythroleukemia cell that can be isolate from mice infected with F-MuLV clone 57. We have designated these cells as 57 TP- 1, indicating their origin from mice infected with F-MuLV clone 57 and their characteristics as transplantable erythroleukemia cells. Upon subcutaneous, intraperitoneal, or intravenous inoculation of these cells, 57 TP-1 cells grow in the hematopoietic organs of the recipient mice. No subcutaneous or intraperitoneal nodules occur. Both F-MuLV and a Friend MCF virus can be detected in these cells, but no evidence to SFFV can be found.

A transcriptional enhancer with specificity for erythroid cells is located in the long terminal repeat of the Friend murine leukemia virus.

“…The Moloney murine leukemia virus (Mo-MuLV) induces T-cell lymphomas after injection into newborn NFS mice, whereas the Friend helper murine leukemia virus (Fr-MuLV) induces primarily erythroleukemia (Tambourin et al, 1979;Oliff et al, 1981;Silver and Fredrickson, 1983). The construction of recombinant viruses demonstrated the existence of a strong determinant of the distinct disease specificities of the two viruses within the U3 region of their long terminal repeats (LTR) (Chatis et al, 1983(Chatis et al, , 1984.…”

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). It was determined that whereas FLC lines established from FV-P-infected spleens contain a high level of spectrin-and a low level of benzidine-positive cells (39), FLC lines from F-MuLV-infected newborn mice contain only spectrin-positive cells, but no benzidine-positive cells (24).…”

“…This cycling of the erythroid precursor cells may render the mouse more susceptible to infection by F-MuLV. The hypothesis that cycling of cells may be important for infection and transformation has previously been proposed, first by Humphries and Temin (38) and more recently by Suzuki and Axelrad (36) and Oliff et al (38).…”

A population of murine hematopoietic progenitors expresses an endogenous retroviral gp70 linked to the Rmcf gene and associated with resistance to erythroleukemia

“…Based on in vitro studies, the presumed mechanism of the restriction of MCF viral replication is blockage of the cell surface MCF viral receptor by endogenous cell surface gp70 (viral interference) (13,14,37) . Erythroleukemia induced by FMuLU can be divided into two stages (38)(39)(40) . The initial step appears to involve hyperplasia of at least two hematopoietic compartments followed by a block in erythroid differentiation .…”