Lower Limb Paralysis Induced in Mice by a Temperature-Sensitive Mutant of Moloney Leukemia Virus2

McCarter, J. A.; Ball, J. K.; Frei, J

doi:10.1093/jnci/59.1.179

Cited by 53 publications

(35 citation statements)

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“…Intracisternal forms of type C retroviral particles have been associated with cytopathology of several disease phenotypes in mice (37)(38)(39)(40)(41), including those observed in prenecrotic CD-1 (3 cells after multidose streptozotocin administration ( 12). Moreover, a correlation between the initiation ofsevere diabetes and induction of these intracellular retroviral particles in cyclophosphamide-induced diabetes in NOD male mice has recently been reported by Suenaga and Yoon (7).…”

Section: Resultsmentioning

confidence: 89%

Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice.

et al. 1992

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Section: Resultsmentioning

confidence: 89%

Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice.

et al. 1992

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“…A variety of murine leukemia viruses (MLVs) are capable of inducing noninflammatory neurodegeneration upon infection of the central nervous system (CNS) (1)(2)(3). Depending on the virus, infected mice exhibit disease with variable incubation periods and clinical severity, initially manifesting as tremulous paralysis that progresses to decerebrate rigidity with associated wasting, which invariably leads to death (4,5).…”

mentioning

confidence: 99%

Ecotropic Murine Leukemia Virus Infection of Glial Progenitors Interferes with Oligodendrocyte Differentiation: Implications for Neurovirulence

Liu

Dunphy

Pedraza

et al. 2016

J Virol

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Certain murine leukemia viruses (MLVs) are capable of inducing fatal progressive spongiform motor neuron disease in mice that is largely mediated by viral Env glycoprotein expression within central nervous system (CNS) glia. While the etiologic mechanisms and the glial subtypes involved remain unresolved, infection of NG2 glia was recently observed to correlate spatially and temporally with altered neuronal physiology and spongiogenesis. Since one role of NG2 cells is to serve as oligodendrocyte (OL) progenitor cells (OPCs), we examined here whether their infection by neurovirulent (FrCasE) or nonneurovirulent (Fr57E) ecotropic MLVs influenced their viability and/or differentiation. Here, we demonstrate that OPCs, but not OLs, are major CNS targets of both FrCasE and Fr57E. We also show that MLV infection of neural progenitor cells (NPCs) in culture did not affect survival, proliferation, or OPC progenitor marker expression but suppressed certain glial differentiation markers. Assessment of glial differentiation in vivo using transplanted transgenic NPCs showed that, while MLVs did not affect cellular engraftment or survival, they did inhibit OL differentiation, irrespective of MLV neurovirulence. In addition, in chimeric brains, where FrCasEinfected NPC transplants caused neurodegeneration, the transplanted NPCs proliferated. These results suggest that MLV infection is not directly cytotoxic to OPCs but rather acts to interfere with OL differentiation. Since both FrCasE and Fr57E viruses restrict OL differentiation but only FrCasE induces overt neurodegeneration, restriction of OL maturation alone cannot account for neuropathogenesis. Instead neurodegeneration may involve a two-hit scenario where interference with OPC differentiation combined with glial Env-induced neuronal hyperexcitability precipitates disease. IMPORTANCEA variety of human and animal retroviruses are capable of causing central nervous system (CNS) neurodegeneration manifested as motor and cognitive deficits. These retroviruses infect a variety of CNS cell types; however, the specific role each cell type plays in neuropathogenesis remains to be established. The NG2 glia, whose CNS functions are only now emerging, are a newly appreciated viral target in murine leukemia virus (MLV)-induced neurodegeneration. Since one role of NG2 glia is that of oligodendrocyte progenitor cells (OPCs), we investigated here whether their infection by the neurovirulent MLV FrCasE contributed to neurodegeneration by affecting OPC viability and/or development. Our results show that both neurovirulent and nonneurovirulent MLVs interfere with oligodendrocyte differentiation. Thus, NG2 glial infection could contribute to neurodegeneration by preventing myelin formation and/or repair and by suspending OPCs in a state of persistent susceptibility to excitotoxic insult mediated by neurovirulent virus effects on other glial subtypes.A variety of murine leukemia viruses (MLVs) are capable of inducing noninflammatory neurodegeneration upon infection of the central ne...

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“…MLV induce a variety of neurological deficiencies depending on the virus isolate and mouse strain (54). One common pathological feature is the induction of spongiform encephalomyelopathy in the CNS and linked deterioration of peripheral motor function (10,11,17,25,34,54); characteristic examples of this include infection of mice with CasBrE, FrCasE, or Moloney ts1 virus (7,33,56) and of rats with PVC-211, NT-40, or A8 virus (5,18,50).…”

mentioning

confidence: 99%

Disparate Regions of Envelope Protein Regulate Syncytium Formation versus Spongiform Encephalopathy in Neurological Disease Induced by Murine Leukemia Virus TR

Murphy

Honczarenko

Dugger

et al. 2004

J Virol

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The murine leukemia virus (MLV) TR1.3 provides an excellent model to study the wide range of retrovirusinduced central nervous system (CNS) pathology and disease. TR1.3 rapidly induces thrombotic events in brain microvessels and causes cell-specific syncytium formation of brain capillary endothelial cells (BCEC). A single amino acid substitution, W102G, in the MLV envelope protein (Env) regulates the pathogenic effects. The role of Env in determining this disease phenotype compared to the induction of spongiform encephalomyelitis with a longer latency, as seen in several other MLV and in human retroviruses, was determined by studying in vitro-attenuated TR1.3. Virus cloned from this selection, termed TRM, induced progressive neurological disease characterized by ataxia and paralysis and the appearance of spongiform neurodegeneration throughout the brain stem and spinal cord. This disease was associated with virus replication in both BCEC and highly ramified glial cells. TRM did not induce syncytium formation, either in vivo or in vitro. Sequence and mutational analyses demonstrated that TRM contained a reversion of Env G102W but that neurological disease mapped to the single amino acid substitution Env S159P. The results demonstrate that single nucleotide changes within disparate regions of Env control dramatically different CNS disease patterns.

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Lower Limb Paralysis Induced in Mice by a Temperature-Sensitive Mutant of Moloney Leukemia Virus2

Cited by 53 publications

References 0 publications

Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice.

Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes-susceptible NOD/Lt from resistant NON/Lt mice.

Ecotropic Murine Leukemia Virus Infection of Glial Progenitors Interferes with Oligodendrocyte Differentiation: Implications for Neurovirulence

Disparate Regions of Envelope Protein Regulate Syncytium Formation versus Spongiform Encephalopathy in Neurological Disease Induced by Murine Leukemia Virus TR

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