Extended self-renewal capacity of pluripotent hemopoietic stem cells: association with persistent Friend spleen focus-forming virus.
The pluripotential hemopoietic stem cells (CFU-S) of genetically resistant Fv2rr adult C57BL/6 (B6) mice can be persistently infected by Friend virus (FV) when exposed to defective spleen focus-forming virus (SFFV) and helper virus (LLV) at the time of transplantation into heavily irradiated syngeneic recipients (that is, B6 leads to B6 isologous chimeras). Whereas normal and LLV+ marrow were depleted of CFU-S after three serial transplantations at 14-day intervals, SFFV+ donor marrow exhibited prolonged self-renewal capacity. SFFV+ CFU-S from B6. Fv2rr chimeric mice gave rise to normal erythroid and myeloid progenitor cells and were easily detected and quantified over 17 serial marrow transfers equivalent to 260 cumulative days. Marrow cellularity on day 14 of each transfer remained constant during the entire transplantation time. When SFFV fell below detectable levels at passage 15, CFU-S self-renewal exhibited rapid and total decline. Since the frequency of LLV-infected cells in late marrow transfers rose during the period of CFU-S decline, we conclude that SFFV is directly associated with the triggering of CFU-S self-renewal. It is also suggested that this proliferative event may be a prerequisite for the development of FV-induced leukemia.
D000818:Animals; D001853:Bone Marrow / Q000382:microbiology / Q000502:physiology; D003114:Colony-Forming Units Assay; D004920:Erythropoiesis; D005622:Friend murine leukemia virus / Q000235:genetics*; D006378:Helper Viruses / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000382:microbiology* / Q000502:physiology; D007942:Leukemia, Experimental / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL