Document Detail


Characterization of an in vitro model of alphavirus infection of immature and mature neurons.
MedLine Citation:
PMID:  15731238     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Terminally differentiated, mature neurons are essential cells that are not easily regenerated. Neurotropic viruses, such as Sindbis virus (SV), cause encephalomyelitis through their ability to replicate in neurons. SV causes the death of immature neurons, while mature neurons can often survive infection. The lack of a reproducible and convenient neuronal cell culture system has hindered a detailed study of the differences in levels of virus replication between immature and mature neurons and the molecular events involved in virus clearance from mature neurons. We have characterized SV replication in immortalized CSM14.1 rat neuronal cells that can be differentiated into neurons. During differentiation, CSM14.1 cells ceased dividing, developed neuronal morphology, and expressed neuron-specific cell markers. SV infection of undifferentiated CSM14.1 cells was efficient and resulted in high levels of virus replication and cell death. SV infection of differentiated CSM14.1 cells was less efficient and resulted in the production of 10- to 100-fold less virus and cell survival. In undifferentiated cells, SV induced a rapid shutdown of cellular protein synthesis and pE2 was efficiently processed to E2 (ratio of E2 to pE2, 2.14). In differentiated cells, the SV-induced shutdown of cellular protein synthesis was transient and pE2 was the primary form of E2 in cells (ratio of E2 to pE2, 0.0426). We conclude that age-dependent restriction of virus replication is an intrinsic property of maturing neurons and that the CSM14.1 cell line is a convenient model system for investigating the interactions of alphaviruses with neurons at various stages of differentiation.
Authors:
Patty S Vernon; Diane E Griffin
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  79     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-25     Completed Date:  2005-04-05     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3438-47     Citation Subset:  IM    
Affiliation:
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Baltimore, MD 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation
Cell Line
Cytopathogenic Effect, Viral
Membrane Glycoproteins / biosynthesis
Neurons / cytology,  virology*
Plaque Assay
Protein Biosynthesis
Protein Precursors / biosynthesis
Proteins / metabolism
Rats
Sindbis Virus / physiology*
Viral Envelope Proteins / biosynthesis
Viral Proteins / biosynthesis
Virus Replication*
Grant Support
ID/Acronym/Agency:
NS38932/NS/NINDS NIH HHS; R01 NS18596/NS/NINDS NIH HHS; T32 GMO7309/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Membrane Glycoproteins; 0/Protein Precursors; 0/Proteins; 0/Viral Envelope Proteins; 0/Viral Proteins; 0/glycoprotein E2, Sindbis virus; 0/glycoprotein PE2, Sindbis virus
Comments/Corrections

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