Effects of murine leukemia virus infection on long-term hematopoiesis in vitro emphasized by increased survival of bone marrow cultures derived from BALB/Mo mice.

The effect of infection with Moloney murine leukemia virus (Mo-MuLV) on long-term bone marrow cultures was studied. Cultures were derived from the bone marrow of BALB/Mo mice, which carry Mo-MuLV as an endogenous virus, or from BALB/c, 129/J, or balb/c X 129/J mice that were infected with Mo-MuLV in vitro. The following parameters were tested: longevity of generation of granulocytes; biological properties of nonadherent cells in colony-forming assays for pluripotential stem cells and committed granulocyte-macrophage colony-forming unit culture, erythroid, or metachromasia-positive mast cell-basophil colony-forming cells; differentiation of nonadherent cells following cocultivation with thymic or bone marrow stromal cells; and generation of WEHI-3 dialyzed conditioned medium-dependent permanent cell lines. Granulocytes were generated for 65 weeks in BALB/Mo marrow cultures, 31 weeks for BALB/c, 22 weeks in 129/J, and 28 weeks in balb/c X 129/J cultures. Exogenous infection of BALB/c cultures with Mo-MuLV increased the longevity of hematopoiesis to 41 weeks. Granulocyte-macrophage colony-forming unit cultures were produced for 61 weeks in BALB/Mo cultures, 25 to 40 weeks in Mo-MuLV-infected cultures, and 19 to 33 weeks in uninfected control cultures. Nonadherent cells harvested from BALB/Mo marrow cultures generated cloned permanent WEHI-3 dialyzed conditioned medium-dependent, nonleukemogenic granulocyte-macrophage colony-forming unit culture cell lines at greater efficiency than did Mo-MuLV-infected or uninfected BALB/c cultures. The cell lines differentiated to mature granulocytes following cocultivation with purified marrow or thymic stromal cells. There was no detectable differentiation of nonadherent cells to lymphocytes or mast cells. Thus, Mo-MuLV does not detectably transform granulocyte progenitor cells in vitro to granulocytic leukemia. However, Mo-MuLV replication stimulates self-renewal of granulocyte progenitor cells in both primary marrow culture and in suspension culture in WEHI-3 dialyzed conditioned medium.