Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chimeric murine oncornavirus FrCas(E) causes a rapidly progressive noninflammatory spongiform encephalomyelopathy after neonatal inoculation. The virus was constructed by the introduction of pol-env sequences from the wild mouse virus CasBrE into the genome of a neuroinvasive but nonneurovirulent strain of Friend murine leukemia virus (FMuLV), FB29. Although the brain infection by FrCas(E) as well as that by other neurovirulent murine retroviruses has been described in detail, little attention has been paid to the neuroinvasive but nonneurovirulent viruses. The purpose of the present study was to compare brain infection by FrCas(E) with that by FB29 and another nonneurovirulent virus, F43, which contains pol-env sequences from FMuLV 57. Both FB29 and F43 infected the same spectrum of cell types in the brain as that infected by FrCas(E), including endothelial cells, microglia, and populations of neurons which divide postnatally. Viral burdens achieved by the two nonneurovirulent viruses in the brain were actually higher than that of FrCas(E). The widespread infection of microglia by the two nonneurovirulent viruses is notable because it is infection of these cells by FrCas(E) which is thought to be a critical determinant of its neuropathogenicity. These results indicate that although the sequence of the envelope gene determines neurovirulence, this effect appears to operate through a mechanism which does not influence either viral tropism or viral burden in the brain. Although all three viruses exhibited similar tropism for granule neurons in the cerebellar cortex, there was a striking difference in the distribution of envelope proteins in those cells in vivo. The FrCas(E) envelope protein accumulated in terminal axons, whereas those of FB29 and F43 remained predominantly in the cell bodies. These observations suggest that differences in the intracellular sorting of these proteins may exist and that these differences appear to correlate with neurovirulence.
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PMID:Brain infection by neuroinvasive but avirulent murine oncornaviruses. 1059 Jan 36

The progressive spongiform encephalomyelopathy caused by ts1, a neuropathogenic temperature-sensitive mutant of Moloney murine leukemia virus (MoMuLV-ts1), results in motor neuronal loss without direct neuronal infection. We have previously reported that ts1-mediated neuronal degeneration in mice has a multifactorial pathogenesis. Here, we report that in the ts1-infected central nervous system (CNS) activated neural cells showed intense immunoreactivity for pro-nerve growth factor (proNGF), neurotrophin receptor p75 (p75(NTR)), and sortilin in the areas showing spongiform changes. Since recent studies suggested that proNGF is more active than mature NGF in inducing neuronal death after binding to co-receptors p75(NTR)/sortilin, we hypothesized that overexpression of proNGF, sortilin and p75(NTR) play a role in ts1-induced neurodegeneration. We found that proNGF and p75(NTR), but not sortilin, mRNA and protein were significantly elevated in ts1-infected brainstem compared to non-infected control tissue. There was extensive tyrosine phosphorylation of p75(NTR), a marker for its activation, in ts1-infected brainstem with abundance in degenerating neurons. We explored whether the increase in the in vivo proNGF expression also occurs in cultured immortalized C1 astrocytes infected by ts1 virus. The proNGF level was significantly increased in infected C1 cells compared to control cells only after addition of fibroblast growth factor (FGF-1). We also showed increased expression of FGF-1 in the CNS of ts1-infected mice. Our findings suggest that the FGF-1 signaling pathway may be responsible for the overexpression of proNGF in neural cells during pathogenesis of ts1-induced neurodegeneration. This study provides new in vivo insights into the possible role of proNGF and its receptors in ts1-induced neurodegeneration.
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PMID:Up-regulation of pro-nerve growth factor, neurotrophin receptor p75, and sortilin is associated with retrovirus-induced spongiform encephalomyelopathy. 1839 88


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