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rdf:type |
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lifeskim:mentions |
umls-concept:C0007600,
umls-concept:C0017262,
umls-concept:C0019704,
umls-concept:C0019721,
umls-concept:C0024264,
umls-concept:C0024432,
umls-concept:C0185117,
umls-concept:C0205147,
umls-concept:C0456387,
umls-concept:C0596988,
umls-concept:C0961954,
umls-concept:C1100939,
umls-concept:C2911684
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pubmed:issue |
1
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pubmed:dateCreated |
2000-1-24
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pubmed:abstractText |
Human macrophage and T cell lines were stably transfected with HIV-1 wild-type Tat or Tat mutants in the cysteine-rich region displaying trans-dominant negative effects on HIV-1 life cycle. The expression of HLA class I and class II molecules was not affected by wild-type Tat. Tat mutants, instead, profoundly down-regulated in a dose-dependent fashion the expression of class II, but not of class I, in both cell types by acting at the transcriptional level. Down-regulation was manifested on constitutive and IFN-gamma-induced class II gene expression and did not correlate with reduced transcription of the AIR-1 gene product CIITA, the major transcriptional activator of class II genes, indicating that Tat mutants did not act by inhibiting AIR-1 gene expression. Class II down-modulation had important functional implications in macrophages, as both antigen processing and presenting capacity were inhibited. These results represent the first evidence that a modified HIV-1 Tat product can act as a potent immunosuppressor by inhibiting the HLA class II expression necessary for triggering both cellular and humoral responses against pathogens. The use of these HIV-1 Tat mutants also discloses new opportunities to investigate the molecular mechanisms underlying the coordinate HLA class II gene transcription.
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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/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, tat,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class II,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/MHC class II transactivator protein,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/tat Gene Products, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0014-2980
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19-28
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10602023-Antigen Presentation,
pubmed-meshheading:10602023-Cell Line,
pubmed-meshheading:10602023-Cysteine,
pubmed-meshheading:10602023-Down-Regulation,
pubmed-meshheading:10602023-Gene Expression Regulation,
pubmed-meshheading:10602023-Gene Products, tat,
pubmed-meshheading:10602023-HIV-1,
pubmed-meshheading:10602023-Histocompatibility Antigens Class I,
pubmed-meshheading:10602023-Histocompatibility Antigens Class II,
pubmed-meshheading:10602023-Humans,
pubmed-meshheading:10602023-Interferon-gamma,
pubmed-meshheading:10602023-Macrophages,
pubmed-meshheading:10602023-Nuclear Proteins,
pubmed-meshheading:10602023-RNA, Messenger,
pubmed-meshheading:10602023-Structure-Activity Relationship,
pubmed-meshheading:10602023-T-Lymphocytes,
pubmed-meshheading:10602023-Trans-Activators,
pubmed-meshheading:10602023-tat Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2000
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pubmed:articleTitle |
HIV-1 Tat mutants in the cysteine-rich region downregulate HLA class II expression in T lymphocytic and macrophage cell lines.
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pubmed:affiliation |
Department of Clinical and Biological Sciences School of Medicine, University of Insubria, Varese, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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