Role of stromal and hematopoietic stem cells in Friend spleen focus forming virus effects in continuous bone marrow culture

Replication of the Friend spleen focus forming virus (SFFV) in C3H/HeJ or C57BL/6J mouse continuous bone marrow cultures is associated with an increased cumulative production of pluripotential/hematopoietic stem cells (CFUs), granulocyte-macrophage progenitor cells (GM-CFUc), and total granulocytes, compared to uninfected or helper virus infected control cultures. The site(s) of action of the virus are not known. To determine whether viral effect(s) occurred in adherent stromal and/or non-adherent hematopoietic stem cells, purified cell populations, comprised exclusively of cells from each compartment, were separated from C57BL/6J (Fv-1^bb) or C3H/HeJ (Fv-1ⁿⁿ) marrow cultures and were left uninfected or were infected with host range replication restricted B-tropic or N-tropic helper pseudotype viruses of SFFV respectively. Cell populations were then mixed to establish continuous hematopoiesis in allogeneic or syngeneic combinations. Virus host range restriction between compartments was maintained in allogeneic reconstituted cultures which showed active hematopoiesis for 16-17 weeks and no significant differences between: (1) virus infected and uninfected groups or (2) groups comprised of stromal cells from one or the other strain. Thus, these data indicate that the prolongation of hematopoiesis in undisturbed long-term marrow cultures by SFFV occurs through an interaction of adherent hematopoietic stem cells with the marrow stroma.