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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0022567,
umls-concept:C0028778,
umls-concept:C0185117,
umls-concept:C0205314,
umls-concept:C0231491,
umls-concept:C0441712,
umls-concept:C0521026,
umls-concept:C0679622,
umls-concept:C1426208,
umls-concept:C1524063,
umls-concept:C1654934,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2009-7-7
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pubmed:abstractText |
Keratinocytes are important for the acute phase of HSV-1 infection and subsequent persistence in sensory nervous tissue. In this study, we showed that keratinocytes (HEL-30) were refractory to IFN-gamma induction of an antiviral state to HSV-1 infection, while IFN-gamma did induce an antiviral state in fibroblasts (L929). This led us to examine the possible role of suppressor of cytokine signaling-1 (SOCS-1) in this refractiveness. RT-PCR analysis of SOCS-1 mRNA expression in HSV-1-infected cells showed a 4-fold increase for keratinocytes while having a negligible effect on fibroblasts. A similar pattern was observed at the level of SOCS-1 protein induction. Activation of STAT1alpha in keratinocytes was inhibited by HSV-1 infection. A direct effect of HSV-1 on the SOCS-1 promoter was shown in a luciferase reporter gene assay. We have developed a small peptide antagonist of SOCS-1, pJAK2(1001-1013), that had both an antiviral effect in keratinocytes against HSV-1 as well as a synergistic effect on IFN-gamma induction of an antiviral state. HSV-1 ICP0 mutant was inhibited by IFN-gamma in HEL-30 cells and was less effective than wild-type virus in induction of SOCS-1 promoter. We conclude that SOCS-1 plays an important role in the inhibition of the antiviral effect of IFN-gamma in keratinocytes infected with HSV-1. The use of SOCS-1 antagonist to abrogate this refractiveness could have a transformational effect on therapy against viral infections.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-10064597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-10479305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-10490100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-10875919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-11756980,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-15187130,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-15558048,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-16000863,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-16051826,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-16174768,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-16381597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-16415872,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-16424886,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-16764725,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-16785443,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-16785527,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-16921466,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-17404288,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-17525754,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-17620742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-17727323,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-17992661,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-18186706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-18197856,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-18250407,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-18551144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-18583567,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-18842720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-18845757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-18945770,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-227796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-2846867,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-3025339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-3318610,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-8910766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-9449714,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-9534953,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19542368-9826711
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1550-6606
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
183
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1253-62
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:19542368-Humans,
pubmed-meshheading:19542368-Immunity,
pubmed-meshheading:19542368-Peptides,
pubmed-meshheading:19542368-RNA, Messenger,
pubmed-meshheading:19542368-Cell Line, Tumor,
pubmed-meshheading:19542368-Promoter Regions, Genetic,
pubmed-meshheading:19542368-Herpesvirus 1, Human,
pubmed-meshheading:19542368-Keratinocytes,
pubmed-meshheading:19542368-Interferon-gamma
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