| pubmed-article:15518810 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15518810 | lifeskim:mentions | umls-concept:C0019704 | lld:lifeskim |
| pubmed-article:15518810 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:15518810 | lifeskim:mentions | umls-concept:C0027882 | lld:lifeskim |
| pubmed-article:15518810 | lifeskim:mentions | umls-concept:C1308752 | lld:lifeskim |
| pubmed-article:15518810 | lifeskim:mentions | umls-concept:C0007587 | lld:lifeskim |
| pubmed-article:15518810 | lifeskim:mentions | umls-concept:C0017280 | lld:lifeskim |
| pubmed-article:15518810 | lifeskim:mentions | umls-concept:C1367714 | lld:lifeskim |
| pubmed-article:15518810 | lifeskim:mentions | umls-concept:C1706327 | lld:lifeskim |
| pubmed-article:15518810 | lifeskim:mentions | umls-concept:C0086597 | lld:lifeskim |
| pubmed-article:15518810 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:15518810 | pubmed:dateCreated | 2004-11-2 | lld:pubmed |
| pubmed-article:15518810 | pubmed:databankReference | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15518810 | pubmed:abstractText | HIV-1 Nef is expressed in astrocytes, but a contribution to neuropathogenesis and the development of HIV-associated dementia (HAD) remains uncertain. To determine the neuropathogenic actions of the HIV-1 Nef protein, the brain-derived (YU-2) and blood-derived (NL4-3) Nef proteins were expressed in neural cells using an alphavirus vector, which resulted in astrocyte death (P < 0.001). Supernatants from Nef-expressing astrocytes also caused neuronal death, suggesting the release of neurotoxic molecules by astrocytes. Analysis of pro-inflammatory gene induction in astrocytes expressing Nef revealed increased IP-10 mRNA expression (4000-fold) that was Nef sequence dependent. Recombinant IP-10 caused selective cell death in neurons (P < 0.001) but not astrocytes, and the cytotoxicity of supernatant from astrocytes expressing Nef YU-2 was blocked by an antibody directed against the chemokine receptor CXCR3 (P < 0.001). SCID/NOD mice implanted with a Nef YU-2-expressing vector displayed abnormal motor behavior (P < 0.05), neuroinflammation, and neuronal loss relative to controls. Analysis of mRNA levels in brains from patients with HAD also revealed increased expression of IP-10 (P < 0.05), which was confirmed by immunoreactivity detected principally in astrocytes. Phylogenetic and protein structure analyses of Nef sequences derived from HIV/AIDS patients with and without HAD suggested viral evolution toward a neurotropic Nef protein. These results indicate that HIV-1 Nef contributes to neuropathogenesis by directly causing astrocyte death together with indirect neuronal death through the cytotoxic actions of IP-10 on neurons. Furthermore, Nef molecular diversity was evident in brain tissue among patients with neurological disease and which may influence IP-10 production by astrocytes. | lld:pubmed |
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| pubmed-article:15518810 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:15518810 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:15518810 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15518810 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:15518810 | pubmed:issn | 0042-6822 | lld:pubmed |
| pubmed-article:15518810 | pubmed:author | pubmed-author:McArthurJusti... | lld:pubmed |
| pubmed-article:15518810 | pubmed:author | pubmed-author:HoldenJanetJ | lld:pubmed |
| pubmed-article:15518810 | pubmed:author | pubmed-author:GillM JohnMJ | lld:pubmed |
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| pubmed-article:15518810 | pubmed:author | pubmed-author:SilvaClaudiaC | lld:pubmed |
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| pubmed-article:15518810 | pubmed:author | pubmed-author:HenryScotS | lld:pubmed |
| pubmed-article:15518810 | pubmed:author | pubmed-author:TodorukTionaT | lld:pubmed |
| pubmed-article:15518810 | pubmed:author | pubmed-author:SullivanAndre... | lld:pubmed |
| pubmed-article:15518810 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15518810 | pubmed:day | 24 | lld:pubmed |
| pubmed-article:15518810 | pubmed:volume | 329 | lld:pubmed |
| pubmed-article:15518810 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15518810 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15518810 | pubmed:pagination | 302-18 | lld:pubmed |
| pubmed-article:15518810 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
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| pubmed-article:15518810 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15518810 | pubmed:articleTitle | Human immunodeficiency virus type 1 Nef protein mediates neural cell death: a neurotoxic role for IP-10. | lld:pubmed |
| pubmed-article:15518810 | pubmed:affiliation | Department of Clinical Neurosciences, University of Calgary, Calgary AB, Canada. | lld:pubmed |
| pubmed-article:15518810 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15518810 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:15518810 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:15518810 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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