| pubmed-article:17416587 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17416587 | lifeskim:mentions | umls-concept:C0019704 | lld:lifeskim |
| pubmed-article:17416587 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:17416587 | lifeskim:mentions | umls-concept:C0026882 | lld:lifeskim |
| pubmed-article:17416587 | lifeskim:mentions | umls-concept:C0332466 | lld:lifeskim |
| pubmed-article:17416587 | lifeskim:mentions | umls-concept:C1707520 | lld:lifeskim |
| pubmed-article:17416587 | lifeskim:mentions | umls-concept:C0913822 | lld:lifeskim |
| pubmed-article:17416587 | lifeskim:mentions | umls-concept:C0913823 | lld:lifeskim |
| pubmed-article:17416587 | pubmed:issue | 23 | lld:pubmed |
| pubmed-article:17416587 | pubmed:dateCreated | 2007-6-4 | lld:pubmed |
| pubmed-article:17416587 | pubmed:abstractText | The loss of CD4(+) T cells in HIV-1 infections is hypothesized to be caused by apoptosis of bystander cells mediated by cell surface-expressed HIV-1 Env glycoprotein. However, the mechanism by which Env mediates this process remains controversial. Specifically, the role of HIV-1 gp120 binding to CD4 and CXCR4 versus the fusion process mediated by gp41 remains unresolved. Env-induced apoptosis in bystander cells has been shown to be gp41-dependent and correlates with the redistribution of membrane lipids between Env-expressing cells and target cells (hemifusion). Using a rational mutagenesis approach aimed at targeting Env function via the gp41 subunit, we examined the role of HIV gp41 in bystander apoptosis. A mutation in the fusion domain of gp41 (V513E) resulted in a fusion-defective Env that failed to induce apoptosis. A mutation in the gp41 N-terminal helix (G547D) reduced cell fusion capacity and apoptosis; conversely, an Env mutant with a deletion of the gp41 cytoplasmic tail (Ct Del) enhanced both cell-to-cell fusion and apoptosis. Most significantly, an Env mutant containing a substitution in the loop region of gp41 (D589L) mediated transfer of lipids (hemifusion) to bystander cells but was defective in cell-to-cell and to a lesser degree virus-to-cell fusion. This mutant was still able to induce apoptosis in bystander cells. Hence, we have provided the first direct evidence that gp41-mediated hemifusion is both required and sufficient for induction of apoptosis in bystander cells. These results may help to explain the mechanism of HIV-1 Env-induced T cell depletion. | lld:pubmed |
| pubmed-article:17416587 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17416587 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17416587 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17416587 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17416587 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17416587 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17416587 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17416587 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17416587 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17416587 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:17416587 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:17416587 | pubmed:author | pubmed-author:FreedEric OEO | lld:pubmed |
| pubmed-article:17416587 | pubmed:author | pubmed-author:BlumenthalRob... | lld:pubmed |
| pubmed-article:17416587 | pubmed:author | pubmed-author:GargHimanshuH | lld:pubmed |
| pubmed-article:17416587 | pubmed:author | pubmed-author:JoshiAnjaliA | lld:pubmed |
| pubmed-article:17416587 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17416587 | pubmed:day | 8 | lld:pubmed |
| pubmed-article:17416587 | pubmed:volume | 282 | lld:pubmed |
| pubmed-article:17416587 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17416587 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17416587 | pubmed:pagination | 16899-906 | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:meshHeading | pubmed-meshheading:17416587... | lld:pubmed |
| pubmed-article:17416587 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17416587 | pubmed:articleTitle | Site-specific mutations in HIV-1 gp41 reveal a correlation between HIV-1-mediated bystander apoptosis and fusion/hemifusion. | lld:pubmed |
| pubmed-article:17416587 | pubmed:affiliation | Membrane Structure and Function Section, Center for Cancer Research Nanobiology Program, NCI, National Institutes of Health, Frederick, Maryland 21702, USA. | lld:pubmed |
| pubmed-article:17416587 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17416587 | pubmed:publicationType | Research Support, N.I.H., Intramural | lld:pubmed |
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