Source:http://linkedlifedata.com/resource/pubmed/id/10201924
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
|
pubmed:dateCreated |
1999-5-13
|
pubmed:abstractText |
Neurons are postmitotic cells that foster virus persistence. These cells lack the HLA class I molecules required for clearance of infected cells. Previously, we showed that HLA class I is induced by measles virus (MV) on glial cells, which is primarily mediated by IFN-beta. In contrast, MV was unable to induce HLA class I or IFN-beta in neuronal cells. This failure was associated with lack of NF-kappa B binding to the positive regulatory domain II element of the IFN-beta promoter, which is essential for virus-induced IFN-beta gene activity. In this study, we demonstrate that the failure to activate NF-kappa B in neuronal cells is due to the inability of MV to induce phosphorylation and degradation of I kappa B, the inhibitor of NF-kappa B. In contrast, TNF-alpha induced degradation of I kappa B alpha in the neuronal cells, suggesting that failure to induce I kappa B alpha degradation is likely due to a defect in virus-mediated signaling rather than to a defect involving neuronal I kappa B alpha. Like MV, mumps virus and dsRNA failed to induce I kappa B alpha degradation in the neuronal cells, suggesting that this defect may be specific to viruses. Autophosphorylation of the dsRNA-dependent protein kinase, a kinase possibly involved in virus-mediated I kappa B alpha phosphorylation, was intact in both cell types. The failure of virus to induce I kappa B alpha phosphorylation and consequently to activate NF-kappa B in neuronal cells could explain the repression of IFN-beta and class I gene expression in virus-infected cells. These findings provide a potential mechanism for the ability of virus to persist in neurons and to escape immune surveillance.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
AIM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/eIF-2 Kinase
|
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
0022-1767
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
1
|
pubmed:volume |
162
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
4024-9
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:10201924-DNA-Binding Proteins,
pubmed-meshheading:10201924-Enzyme Activation,
pubmed-meshheading:10201924-Humans,
pubmed-meshheading:10201924-I-kappa B Proteins,
pubmed-meshheading:10201924-Measles virus,
pubmed-meshheading:10201924-Mumps virus,
pubmed-meshheading:10201924-NF-kappa B,
pubmed-meshheading:10201924-Neuroglia,
pubmed-meshheading:10201924-Neurons,
pubmed-meshheading:10201924-Phosphorylation,
pubmed-meshheading:10201924-Protein Binding,
pubmed-meshheading:10201924-Signal Transduction,
pubmed-meshheading:10201924-Tumor Cells, Cultured,
pubmed-meshheading:10201924-Ultraviolet Rays,
pubmed-meshheading:10201924-eIF-2 Kinase
|
pubmed:year |
1999
|
pubmed:articleTitle |
Failure of measles virus to activate nuclear factor-kappa B in neuronal cells: implications on the immune response to viral infections in the central nervous system.
|
pubmed:affiliation |
Department of Neurology, University of Maryland at Baltimore, MD 21201, USA. sjalbut@umaryland.edu
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
|