Suppression of Rat Bone Marrow Cells by Friend Murine Leukemia Virus Envelope Proteins

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.

Identification of Genetic Determinants That Regulate Tumorigenicity of Friend Murine Leukemia Virus in Rats

“…However, it is unlikely, because FB29 virus, which does not contain the FVb1 motif ( Fig. 4), has very low or no leukemogenicity in rats (17). Therefore, we were able to demonstrate that the contribution of the enhancer region, and in particular the FVa motifs, is important in the induction of thymoma in rats.…”

“…It has been reported that PVC211, FB29 and NT40 do not induce leukemia in rats, as they do in mice (16,17,23,25). However, clone A8 has high leukemogenic potential against both mice and rats (25).…”

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Friend murine leukemia virus (FrMLV) clone A8 causes a progressive neurodegenerative disease when the virus is inoculated into newborn rats in addition to the related clones PVC211 and FB29, and of a variant, NT40, derived from FB29 (5,16,24). It has been reported that PVC211, FB29 and NT40 do not induce leukemia in rats, as they do in mice (16,17,23,25). However, clone A8 has high leukemogenic potential against both mice and rats (25).

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Abundant Defective Viral Particles Budding from Microglia in the Course of Retroviral Spongiform Encephalopathy

“…Purification, subsequent immunostaining, immunoblotting, and cytofluorometric analyses of microglia and of peritoneal macrophages were performed as described in detail before (5,14,25). Briefly, brains were removed from perfused animals, stripped of meninges, enzymatically digested, and subjected to density gradient centrifugation.…”

“…mRNA was isolated from cells and tissues, employing oligo(dT) 25 Dynabeads following the recommendations of the manufacturer (Dynal). After Northern blotting, blots were probed with a viral envelope-specific 32 P-labeled probe (14) as well as with a 32 P-labeled probe for a housekeeping gene, rat glyceraldehyde-3-phosphate dehydrogenase.…”