1
40
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Text
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<a href="http://doi.org/10.1128/jvi.74.3.1558-1565.2000" target="_blank" rel="noreferrer noopener">http://doi.org/10.1128/jvi.74.3.1558-1565.2000</a>
Pages
1558–1565
Issue
3
Volume
74
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Differential glycosylation of the Cas-Br-E env protein is associated with retrovirus-induced spongiform neurodegeneration.
Publisher
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Journal of virology
Date
A point or period of time associated with an event in the lifecycle of the resource
2000
2000-02
Subject
The topic of the resource
Animals; Brain/metabolism/*pathology/*virology; Gammaretrovirus/genetics/metabolism/*pathogenicity; Glycosylation; Mice; Protein Isoforms; Retroviridae Infections/pathology/*virology; Viral Envelope Proteins/chemistry/genetics/*metabolism
Creator
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Lynch W P; Sharpe A H
Description
An account of the resource
The wild mouse ecotropic retrovirus, Cas-Br-E, induces progressive, noninflammatory spongiform neurodegenerative disease in susceptible mice. Functional genetic analysis of the Cas-Br-E genome indicates that neurovirulence maps to the env gene, which encodes the surface glycoprotein responsible for binding and fusion of virus to host cells. To understand how the envelope protein might be involved in the induction of disease, we examined the regional and temporal expression of Cas-Br-E Env protein in the central nervous systems (CNS) of mice infected with the highly neurovirulent chimeric virus FrCas(E). We observed that multiple isoforms of Cas-Br-E Env were expressed in the CNS, with different brain regions exhibiting unique patterns of processed Env glycoprotein. Specifically, the expression of gp70 correlated with regions showing microglial infection and spongiform neurodegeneration. In contrast, regions high in neuronal infection and without neurodegenerative changes (the cerebellum and olfactory bulb) were characterized by a gp65 Env protein isoform. Sedimentation analysis of brain region extracts indicated that gp65 rather than gp70 was incorporated into virions. Biochemical analysis of the Cas-Br-E Env isoforms indicated that they result from differential processing of N-linked sugars. Taken together, these results indicate that differential posttranslational modification of the Cas-Br-E Env is associated with a failure to incorporate certain Env isoforms into virions in vivo, suggesting that defective viral assembly may be associated with the induction of spongiform neurodegeneration.
Identifier
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<a href="http://doi.org/10.1128/jvi.74.3.1558-1565.2000" target="_blank" rel="noreferrer noopener">10.1128/jvi.74.3.1558-1565.2000</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2000
Animals
Brain/metabolism/*pathology/*virology
Gammaretrovirus/genetics/metabolism/*pathogenicity
Glycosylation
Journal of virology
Lynch W P
Mice
Protein Isoforms
Retroviridae Infections/pathology/*virology
Sharpe A H
Viral Envelope Proteins/chemistry/genetics/*metabolism
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Pages
6841–6851
Issue
8
Volume
73
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Neural stem cells as engraftable packaging lines can mediate gene delivery to microglia: evidence from studying retroviral env-related neurodegeneration.
Publisher
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Journal of virology
Date
A point or period of time associated with an event in the lifecycle of the resource
1999
1999-08
Subject
The topic of the resource
Animals; Mice; Cell Line; *Gene Transfer Techniques; Retroviridae Infections/pathology/*virology; *Microglia/cytology; *Stem Cells/cytology; Hematopoietic Stem Cell Transplantation; Nerve Degeneration; Retroviridae/genetics/*physiology; *Genes; env
Creator
An entity primarily responsible for making the resource
Lynch W P; Sharpe A H; Snyder E Y
Description
An account of the resource
The induction of spongiform myeloencephalopathy by murine leukemia viruses is mediated primarily by infection of central nervous system (CNS) microglia. In this regard, we have previously shown that CasBrE-induced disease requires late, rather than early, virus replication events in microglial cells (W. P. Lynch et al., J. Virol. 70:8896-8907, 1996). Furthermore, neurodegeneration requires the presence of unique sequences within the viral env gene. Thus, the neurodegeneration-inducing events could result from microglial expression of retroviral envelope protein alone or from the interaction of envelope protein with other viral structural proteins in the virus assembly and maturation process. To distinguish between these possible mechanisms of disease induction, we engineered the engraftable neural stem cell line C17-2 into packaging/producer cells in order to deliver the neurovirulent CasBrE env gene to endogenous CNS cells. This strategy resulted in significant CasBrE env expression within CNS microglia without the appearance of replication competent virus. CasBrE envelope expression within microglia was accompanied by increased expression of activation markers F4/80 and Mac-1 (CD11b) but failed to induce spongiform neurodegenerative changes. These results suggest that envelope expression alone within microglia is not sufficient to induce neurodegeneration. Rather, microglia-mediated disease appears to require neurovirulent Env protein interaction with other viral proteins during assembly or maturation. More broadly, the results presented here prove the efficacy of a novel method by which neural stem cell biology may be harnessed for genetically manipulating the CNS, not only for studying neurodegeneration but also as a paradigm for the disseminated distribution of retroviral vector-transduced genes.
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Gene Transfer Techniques
*Genes
*Microglia/cytology
*Stem Cells/cytology
1999
Animals
Cell Line
env
Hematopoietic Stem Cell Transplantation
Journal of virology
Lynch W P
Mice
Nerve Degeneration
Retroviridae Infections/pathology/*virology
Retroviridae/genetics/*physiology
Sharpe A H
Snyder E Y