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Suppression of rat bone marrow cells by Friend murine leukemia virus envelope proteins
S Mazgareanu1, J G Müller, S Czub
1Institut für Virologie und Immunbiologie, Universität Würzburg, Germany.
Abstract:
In a retroviral rat model, we have investigated the nontransforming effects of murine leukemia virus FB29 on the bone marrow. Upon intraperitoneal 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 persistent 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 211, 408-417). Exposure to virus irreversibly decreased numbers of bone marrow cells staining with monoclonal antibody OX7 by 10-30%. Reduction of OX7+ bone marrow cells by 20% was also observed in vitro, after bone marrow cells from uninfected adult rats had been co-incubated with virus. FB29-envelope proteins were sufficient alone to reduce numbers of OX7+ bone marrow cells, both in vivo and in vitro. According to results on incorporation of propidium iodide, decreased numbers of OX7+ cells were due to cell death. By flow cytometric analyses OX7+ bone marrow cells as well as monocytes/macrophages were identified to be major target cells for infection with FB29 within the bone marrow. Thus, the mechanism(s) responsible for death of OX7+ bone marrow cells might be due to direct toxicity of viral envelope proteins and/or to interactions of viral envelope proteins with cells of the monocytic lineage.
Insights
Murine leukemia virus FB29 infects rat bone marrow cells, causing cell death in OX7+ cells and monocytes/macrophages. Neonatal rats develop persistent infection, while adults clear it via immune response.
Area of Science:
- * Virology
- * Immunology
- * Hematology
Background:
- * Murine leukemia virus (MuLV) FB29 is a nontransforming retrovirus.
- * Bone marrow is a critical site for hematopoiesis and immune cell development.
Purpose of the Study:
- * To investigate the effects of MuLV FB29 infection on rat bone marrow.
- * To identify target cells and mechanisms of MuLV FB29-induced bone marrow pathology.
Main Methods:
- * Intraperitoneal inoculation of neonatal and adult rats with MuLV FB29.
- * In vitro co-incubation of rat bone marrow cells with MuLV FB29.
- * Flow cytometry and propidium iodide staining to assess cell viability and identify cell populations.
- * Analysis of OX7+ bone marrow cells and monocytes/macrophages.
Main Results:
- * MuLV FB29 caused massive bone marrow infection within 12 days post-inoculation.
- * Neonatal rats developed persistent infection; adult rats cleared the infection.
- * Exposure to MuLV FB29 irreversibly reduced OX7+ bone marrow cells by 10-30% in vivo and 20% in vitro.
- * Viral envelope proteins alone were sufficient to reduce OX7+ cells, indicating direct toxicity.
- * OX7+ bone marrow cells and monocytes/macrophages were identified as major target cells for FB29 infection.
- * Cell death was confirmed by propidium iodide incorporation.
Conclusions:
- * MuLV FB29 infection leads to significant depletion of OX7+ bone marrow cells and monocytes/macrophages.
- * Viral envelope protein toxicity and/or interactions with monocytic cells mediate FB29-induced bone marrow cell death.
- * Host immune response plays a crucial role in clearing retroviral infection in adult rats.