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rdf:type |
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lifeskim:mentions |
umls-concept:C0011065,
umls-concept:C0017262,
umls-concept:C0019704,
umls-concept:C0185117,
umls-concept:C0205263,
umls-concept:C0441712,
umls-concept:C1366876,
umls-concept:C1833235,
umls-concept:C1979930,
umls-concept:C2728259,
umls-concept:C2911684
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pubmed:issue |
23
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pubmed:dateCreated |
2008-11-12
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pubmed:abstractText |
Chronic viral infection is characterized by the functional impairment of virus-specific T-cell responses. Recent evidence has suggested that the inhibitory receptor programmed death 1 (PD-1) is specifically upregulated on antigen-specific T cells during various chronic viral infections. Indeed, it has been reported that human immunodeficiency virus (HIV)-specific T cells express elevated levels of PD-1 and that this expression correlates with the viral load and inversely with CD4(+) T-cell counts. More importantly, antibody blockade of the PD-1/PD-L1 pathway was sufficient to both increase and stimulate virus-specific T-cell proliferation and cytokine production. However, the mechanisms that mediate HIV-induced PD-1 upregulation are not known. Here, we provide evidence that the HIV type 1 (HIV-1) accessory protein Nef can transcriptionally induce the expression of PD-1 during infection in vitro. Nef-induced PD-1 upregulation requires its proline-rich motif and the activation of the downstream kinase p38. Further, inhibition of Nef activity by p38 MAPK inhibitor effectively blocked PD-1 upregulation, suggesting that p38 MAPK activation is an important initiating event in Nef-mediated PD-1 expression in HIV-1-infected cells. These data demonstrate an important signaling event of Nef in HIV-1 pathogenesis.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-10371163,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-10485649,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-10525088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-10644378,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-11015443,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-11222724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-11224527,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-12853962,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-15668739,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-15928037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-16382236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-16429131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-16760313,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-16917489,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-16921384,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-16954372,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-17000870,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-17182670,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-17287266,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-17376899,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-17641065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-17906628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-18173375,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-18389475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-2032289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-7474080,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-7481804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-7808489,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-7859737,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-8804432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-9450757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-9658095,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18799583-9790524
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PDCD1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Programmed Cell Death 1 Receptor,
http://linkedlifedata.com/resource/pubmed/chemical/nef Gene Products, Human...,
http://linkedlifedata.com/resource/pubmed/chemical/nef protein, Human...,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1098-5514
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pubmed:author |
pubmed-author:ChooAndrew YAY,
pubmed-author:ChungChristopher WCW,
pubmed-author:HiraoLaurenL,
pubmed-author:LaddyDominick JDJ,
pubmed-author:LankaramanKarthikbabu MKM,
pubmed-author:MuthumaniKaruppiahK,
pubmed-author:ShedlockDevon JDJ,
pubmed-author:SilvestriGuidoG,
pubmed-author:SundaramSenthil GSG,
pubmed-author:TebasPabloP,
pubmed-author:ThieuKhanh PKP,
pubmed-author:WeinerDavid BDB,
pubmed-author:WuLingL
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pubmed:issnType |
Electronic
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pubmed:volume |
82
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11536-44
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18799583-Acquired Immunodeficiency Syndrome,
pubmed-meshheading:18799583-Antigens, CD,
pubmed-meshheading:18799583-Apoptosis Regulatory Proteins,
pubmed-meshheading:18799583-CD4-Positive T-Lymphocytes,
pubmed-meshheading:18799583-Cells, Cultured,
pubmed-meshheading:18799583-Gene Expression Regulation,
pubmed-meshheading:18799583-Humans,
pubmed-meshheading:18799583-Programmed Cell Death 1 Receptor,
pubmed-meshheading:18799583-Up-Regulation,
pubmed-meshheading:18799583-nef Gene Products, Human Immunodeficiency Virus,
pubmed-meshheading:18799583-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2008
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pubmed:articleTitle |
Human immunodeficiency virus type 1 Nef induces programmed death 1 expression through a p38 mitogen-activated protein kinase-dependent mechanism.
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pubmed:affiliation |
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. muthuman@mail.med.upenn.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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