rdf:type |
|
lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0017337,
umls-concept:C0017968,
umls-concept:C0040995,
umls-concept:C0185117,
umls-concept:C0205087,
umls-concept:C0206679,
umls-concept:C0871261,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911684,
umls-concept:C2911692
|
pubmed:issue |
17
|
pubmed:dateCreated |
2010-8-6
|
pubmed:abstractText |
Following herpes simplex virus type 1 (HSV-1) ocular infection of C57BL/6 mice, activated CD8(+) T cells specific for an immunodominant epitope on HSV-1 glycoprotein B (gB-CD8 cells) establish a stable memory population in HSV-1 latently infected trigeminal ganglia (TG), whereas non-HSV-specific CD8(+) T cells are lost over time. The retention and activation of gB-CD8 cells appear to be influenced by persistent viral antigenic exposure within the latently infected TG. We hypothesized that the low-level expression of gB from its native promoter before viral DNA synthesis is critical for the retention and activation of gB-CD8 cells in the TG during HSV-1 latency and for their ability to block HSV-1 reactivation from latency. To test this, we created a recombinant HSV-1 in which gB is expressed only after viral DNA synthesis from the true late gC promoter (gCp-gB). Despite minor growth differences compared to its rescuant in infected corneas, gCp-gB was significantly growth impaired in the TG and produced a reduced latent genome load. The gCp-gB- and rescuant-infected mice mounted similar gB-CD8 effector responses, but the size and activation phenotypes of the memory gB-CD8 cells were diminished in gCp-gB latently infected TG, suggesting that the stimulation of gB-CD8 cells requires gB expression before viral DNA synthesis. Surprisingly, late gB expression did not compromise the capacity of gB-CD8 cells to inhibit HSV-1 reactivation from latency in ex vivo TG cultures, suggesting that gB-CD8 cells can block HSV-1 reactivation at a very late stage in the viral life cycle. These data have implications for designing better immunogens for vaccines to prevent HSV-1 reactivation.
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pubmed:grant |
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-10438852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-10790421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-11602757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-11773630,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-12551982,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-1312625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-14633592,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-16051826,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-1654309,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-17229688,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-17360672,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-9420303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20573821-9445016
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Sep
|
pubmed:issn |
1098-5514
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pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:volume |
84
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
8811-20
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pubmed:dateRevised |
2011-7-25
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pubmed:meshHeading |
pubmed-meshheading:20573821-Animals,
pubmed-meshheading:20573821-CD8-Positive T-Lymphocytes,
pubmed-meshheading:20573821-Cercopithecus aethiops,
pubmed-meshheading:20573821-Female,
pubmed-meshheading:20573821-Gene Expression Regulation, Viral,
pubmed-meshheading:20573821-Herpes Simplex,
pubmed-meshheading:20573821-Herpesvirus 1, Human,
pubmed-meshheading:20573821-Humans,
pubmed-meshheading:20573821-Mice,
pubmed-meshheading:20573821-Mice, Inbred C57BL,
pubmed-meshheading:20573821-Trigeminal Ganglion,
pubmed-meshheading:20573821-Vero Cells,
pubmed-meshheading:20573821-Viral Envelope Proteins,
pubmed-meshheading:20573821-Virulence
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pubmed:year |
2010
|
pubmed:articleTitle |
Delaying the expression of herpes simplex virus type 1 glycoprotein B (gB) to a true late gene alters neurovirulence and inhibits the gB-CD8+ T-cell response in the trigeminal ganglion.
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pubmed:affiliation |
Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|