| pubmed-article:19805909 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C0019682 | lld:lifeskim |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C0019699 | lld:lifeskim |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C0026336 | lld:lifeskim |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C0178539 | lld:lifeskim |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C0220908 | lld:lifeskim |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C1555029 | lld:lifeskim |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C0205225 | lld:lifeskim |
| pubmed-article:19805909 | lifeskim:mentions | umls-concept:C0205198 | lld:lifeskim |
| pubmed-article:19805909 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:19805909 | pubmed:dateCreated | 2009-11-3 | lld:pubmed |
| pubmed-article:19805909 | pubmed:abstractText | The development of highly active antiretroviral therapy (HAART) to treat individuals infected with HIV-1 has dramatically improved patient outcomes, but HAART still fails to cure the infection. The latent viral reservoir in resting CD4+ T cells is a major barrier to virus eradication. Elimination of this reservoir requires reactivation of the latent virus. However, strategies for reactivating HIV-1 through nonspecific T cell activation have clinically unacceptable toxicities. We describe here the development of what we believe to be a novel in vitro model of HIV-1 latency that we used to search for compounds that can reverse latency. Human primary CD4+ T cells were transduced with the prosurvival molecule Bcl-2, and the resulting cells were shown to recapitulate the quiescent state of resting CD4+ T cells in vivo. Using this model system, we screened small-molecule libraries and identified a compound that reactivated latent HIV-1 without inducing global T cell activation, 5-hydroxynaphthalene-1,4-dione (5HN). Unlike previously described latency-reversing agents, 5HN activated latent HIV-1 through ROS and NF-kappaB without affecting nuclear factor of activated T cells (NFAT) and PKC, demonstrating that TCR pathways can be dissected and utilized to purge latent virus. Our study expands the number of classes of latency-reversing therapeutics and demonstrates the utility of this in vitro model for finding strategies to eradicate HIV-1 infection. | lld:pubmed |
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| pubmed-article:19805909 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19805909 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19805909 | pubmed:citationSubset | AIM | lld:pubmed |
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