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40
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Text
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URL Address
<a href="http://doi.org/10.1186/1742-4690-7-93" target="_blank" rel="noreferrer noopener">http://doi.org/10.1186/1742-4690-7-93</a>
Pages
93–93
Volume
7
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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Misfolding of CasBrE SU is reversed by interactions with 4070A Env: implications for gammaretroviral neuropathogenesis.
Publisher
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Retrovirology
Date
A point or period of time associated with an event in the lifecycle of the resource
2010
2010-11
Subject
The topic of the resource
Animals; Cell Line; env/*metabolism; Experimental/*virology; Gene Products; Helper Viruses/metabolism/pathogenicity/*physiology; Leukemia; Leukemia Virus; Mice; Motor Neuron Disease/*virology; Murine/metabolism/pathogenicity/*physiology; Neural Stem Cells/*virology; Protein Binding; Protein Folding; Protein Subunits/metabolism; Retroviridae Infections/*virology; Tumor Virus Infections/*virology; Virulence
Creator
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Li Ying; Lynch William P
Description
An account of the resource
BACKGROUND: CasBrE is a neurovirulent murine leukemia virus (MLV) capable of inducing paralytic disease with associated spongiform neurodegeneration. The neurovirulence of this virus has been genetically mapped to the surface expressed subunit (SU) of the env gene. However, CasBrE SU synthesized in the absence of the transmembrane subunit (TM) does not retain ecotropic receptor binding activity, indicating that folding of the receptor binding domain (RBD) requires this domain. Using a neural stem cell (NSC) based viral trans complementation approach to examine whether misfolded CasBrE SU retained neurovirulence, we observed CasBrE SU interaction with the "non-neurovirulent" amphotropic helper virus, 4070A which restored functional activity of CasBrE SU. RESULTS: Herein, we show that infection of NSCs expressing CasBrE SU with 4070A (CasES+4070A-NSCs) resulted in the redistribution of CasBrE SU from a strictly secreted product to include retention on the plasma membrane. Cell surface cross-linking analysis suggested that CasBrE SU membrane localization was due to interactions with 4070A Env. Viral particles produced from CasES+4070A-NSCS contained both CasBrE and 4070A gp70 Env proteins. These particles displayed ecotropic receptor-mediated infection, but were still 100-fold less efficient than CasE+4070A-NSC virus. Infectious center analysis showed CasBrE SU ecotropic transduction efficiencies approaching those of NSCs expressing full length CasBrE Env (CasE; SU+TM). In addition, CasBrE SU-4070A Env interactions resulted in robust ecotropic superinfection interference indicating near native intracellular SU interaction with its receptor, mCAT-1. CONCLUSIONS: In this report we provided evidence that 4070A Env and CasBrE SU physically interact within NSCs leading to CasBrE SU retention on the plasma membrane, incorporation into viral particles, restoration of mCAT-1 binding, and capacity for initiation of TM-mediated fusion events. Thus, heterotropic Env-SU interactions facilitates CasBrE SU folding events that restore Env activity. These findings are consistent with the idea that one protein conformation acts as a folding scaffold or nucleus for a second protein of similar primary structure, a process reminiscent of prion formation. The implication is that template-based protein folding may represent an inherent feature of neuropathogenic proteins that extends to retroviral Envs.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1186/1742-4690-7-93" target="_blank" rel="noreferrer noopener">10.1186/1742-4690-7-93</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).
2010
Animals
Cell Line
Department of Integrative Medical Sciences
env/*metabolism
Experimental/*virology
Gene Products
Helper Viruses/metabolism/pathogenicity/*physiology
Leukemia
Leukemia Virus
Li Ying
Lynch William P
Mice
Motor Neuron Disease/*virology
Murine/metabolism/pathogenicity/*physiology
NEOMED College of Medicine
Neural Stem Cells/*virology
Protein Binding
Protein Folding
Protein Subunits/metabolism
Retroviridae Infections/*virology
Retrovirology
Tumor Virus Infections/*virology
Virulence
-
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.
URL Address
<a href="http://doi.org/10.1128/JVI.03156-15" target="_blank" rel="noreferrer noopener">http://doi.org/10.1128/JVI.03156-15</a>
Pages
3385–3399
Issue
7
Volume
90
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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Ecotropic Murine Leukemia Virus Infection of Glial Progenitors Interferes with Oligodendrocyte Differentiation: Implications for Neurovirulence.
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
2016
2016-01
Subject
The topic of the resource
3T3 Cells; Animals; Cell Line; Cell Proliferation; Cell Survival; env/biosynthesis; Female; Gene Products; Leukemia Virus; Male; Mice; Motor Neuron Disease/*virology; Murine/*pathogenicity; Neural Stem Cells/*virology; Neurogenesis/*physiology; Neuroglia/*virology; Oligodendroglia/cytology/virology; Retroviridae Infections/*complications; Transgenic
Creator
An entity primarily responsible for making the resource
Li Ying; Dunphy Jaclyn M; Pedraza Carlos E; Lynch Connor R; Cardona Sandra M; Macklin Wendy B; Lynch William P
Description
An account of the resource
UNLABELLED: 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 FrCasE-infected 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. IMPORTANCE: A 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.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1128/JVI.03156-15" target="_blank" rel="noreferrer noopener">10.1128/JVI.03156-15</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).
2016
3T3 Cells
Animals
Cardona Sandra M
Cell Line
Cell Proliferation
Cell Survival
Department of Integrative Medical Sciences
Dunphy Jaclyn M
env/biosynthesis
Female
Gene Products
Journal of virology
Leukemia Virus
Li Ying
Lynch Connor R
Lynch William P
Macklin Wendy B
Male
Mice
Motor Neuron Disease/*virology
Murine/*pathogenicity
NEOMED College of Medicine
Neural Stem Cells/*virology
Neurogenesis/*physiology
Neuroglia/*virology
Oligodendroglia/cytology/virology
Pedraza Carlos E
Retroviridae Infections/*complications
Transgenic