SUPPRESSION OF RAT BONE-MARROW CELLS BY FRIEND MURINE LEUKEMIA-VIRUS ENVELOPE PROTEINS

In a retroviral rat model, we have investigated the nontransforming ef fects of murine leukemia virus FB29 on the bone marrow. Upon intraperi toneal inoculation with murine leukemia virus FB29 of either neonatal or adult rats, bone marrow cells became massively infected within the first 12 days postinoculation. In neonatally inoculated rats, a persis tent productive bone marrow infection was established, whereas in rats inoculated as adults, no infected bone marrow cells could be detected beyond 12 days postinoculation. Retroviral infection was most likely cleared by an antiviral immune response (Hein et al., 1995, Virology 2 11, 408-417). Exposure to virus irreversibly decreased numbers of bone marrow cells staining with monoclonal antibody OX7 by 10-30%. Reducti on of OX7(+) bone marrow cells by 20% was also observed in vitro after bone marrow cells from uninfected adult rats had been co-incubated wi th virus. FB29-envelope proteins were sufficient alone to reduce numbe rs of OX7(+) bone marrow cells, both in vivo and in vitro. According t o results on incorporation of propidium iodide, decreased numbers of O X7+ cells were due to cell death. By flow cytometric analyses OX7(+) b one marrow cells as well as monocytes/macrophages were identified to b e major target cells for infection with FB29 within the bone marrow. T hus, the mechanism(s) responsible for death of OX7(+) bone marrow cell s might be due to direct toxicity of viral envelope proteins and/or to interactions of viral envelope proteins with cells of the monocytic l ineage. (C) 1998 Academic Press.