Linked Life Data

11298454

Source:http://linkedlifedata.com/resource/pubmed/id/11298454

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6830
pubmed:dateCreated
2001-4-12
pubmed:abstractText
In vivo infection of lymphatic tissues by the human immunodeficiency virus type 1 (HIV-1) leads to enhanced apoptosis, which prominently involves uninfected bystander cells. Increased killing of such bystander cells is mediated in part through Nef induction of Fas ligand (FasL) expression on the surface of the virally infected T cells. The subsequent interaction of FasL with Fas (CD95) displayed on neighbouring cells, including HIV-1-specific cytotoxic T lymphocytes, may lead to bystander cell killing and thus forms an important mechanism of immune evasion. As HIV-1 also enhances Fas expression on virally infected cells, it is unclear how these hosts avoid rapid cell-autonomous apoptosis mediated through cis ligation of Fas by FasL. Here we show that HIV-1 Nef associates with and inhibits apoptosis signal-regulating kinase 1 (ASK1), a serine/threonine kinase that forms a common and key signalling intermediate in the Fas and tumour-necrosis factor-alpha (TNFalpha) death-signalling pathways. The interaction of Nef with ASK1 inhibits both Fas- and TNFalpha-mediated apoptosis, as well as the activation of the downstream c-Jun amino-terminal kinase. Our findings reveal a strategy by which HIV-1 Nef promotes the killing of bystander cells through the induction of FasL, while simultaneously protecting the HIV-1-infected host cell from these same pro-apoptotic signals through its interference with ASK1 function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein, http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, nef, http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 5, http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases, http://linkedlifedata.com/resource/pubmed/chemical/MAP3K5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 8, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0028-0836
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
410
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
834-8
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell.
pubmed:affiliation
Gladstone Institute of Virology and Immunology, PO Box 419100, San Francisco, California 94141-9100, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't