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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
2006-11-13
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pubmed:abstractText |
Epstein-Barr virus (EBV) establishes a persistent infection in the human host and is associated with a variety of human cancers. Persistent infection results from a balance between the host immune response and viral immune evasion mechanisms. EBV infection is controlled initially by the innate immune response and later by T-cell-mediated adaptive immunity. EBV has evolved mechanisms to evade the host immune response so that it can persist for the lifetime of the host. Latent membrane protein 1 (LMP-1) is the EBV oncoprotein essential for B-cell immortalization by EBV. We show here that LMP-1 interacts with Tyk2, a signaling intermediate in the alpha interferon (IFN-alpha) signaling pathway, via a previously uncharacterized LMP-1 signaling domain. LMP-1 prevents Tyk2 phosphorylation and inhibits IFN-alpha-stimulated STAT2 nuclear translocation and interferon-stimulated response element transcriptional activity. Long-term culture of EBV+ lymphoblastoid cells in IFN-alpha is associated with outgrowth of a population expressing elevated LMP-1 protein levels, suggesting that cells expressing higher levels of LMP-1 survive the antiproliferative selective pressure imposed by IFN-alpha. These results show that LMP-1 can protect EBV+ cells from the IFN-alpha-stimulated antiviral/antiproliferative response and suggest that chronic IFN-alpha treatment may encourage the outgrowth of cells expressing elevated, and therefore potentially oncogenic, LMP-1 levels in EBV+ individuals.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-10082588,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-10195428,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-10357818,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-10523853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-10627515,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-11000250,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-11070173,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-11070174,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-11119603,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-11536044,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-11711629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-11815625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-11867523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-12391177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-12401515,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-12574168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-12592401,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-12610149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-12884916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-12928589,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-1321292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-1406670,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-14747531,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-15308723,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-15507648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-15795279,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-15864272,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-16083776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-16469740,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-1667088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-1827846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-2542565,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-2581792,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-2836780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-2953024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-3035211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-3039344,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-6161964,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-6302703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-6321354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-7528775,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-8045261,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-8415670,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-8688561,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-8780896,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-8943365,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-9001242,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-9234942,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-9261415,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-9315633,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-9359753,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16987978-9501091
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-538X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
80
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11638-50
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16987978-B-Lymphocytes,
pubmed-meshheading:16987978-Gene Expression Regulation, Viral,
pubmed-meshheading:16987978-Herpesvirus 4, Human,
pubmed-meshheading:16987978-Humans,
pubmed-meshheading:16987978-Interferons,
pubmed-meshheading:16987978-Phosphorylation,
pubmed-meshheading:16987978-Signal Transduction,
pubmed-meshheading:16987978-TYK2 Kinase,
pubmed-meshheading:16987978-Tumor Cells, Cultured,
pubmed-meshheading:16987978-Viral Matrix Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
The Epstein-Barr virus-encoded LMP-1 oncoprotein negatively affects Tyk2 phosphorylation and interferon signaling in human B cells.
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pubmed:affiliation |
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Campus Box 347, Boulder, CO 80309, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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