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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-9-15
pubmed:abstractText
Infection of macrophages (M/M) by human immunodeficiency virus (HIV) is a main pathogenetic event leading to neuronal dysfunction and death in patients with AIDS dementia complex. Alteration of viability of neurons and astrocytes occurs in vivo even without their infection, thus it is conceivable that HIV-infected M/M may affect viability of such cells even without direct infection. To assess this hypothesis, we studied the effects of HIV-infected M/M on an astrocytic cell-line lacking CD4-receptor expression. Exposure to supernatants of HIV-infected M/M triggers complete disruption and apoptotic death of astrocytic cells. This effect is not related to HIV transmission from infected M/M, because HIV-DNA and p24 production in astrocytic cells remained negative. Apoptotic death of astrocytes is mainly mediated by Fas ligand released in supernatants of HIV-infected M/M (as demonstrated by complete reversal of such phenomenon by adding neutralizing antibodies against CD95 receptor). Treatment of astrocytic cells with recombinant (biologically active) Tat induces < 10% apoptosis, and gp120 was totally ineffective. Treatment of HIV-infected M/M with AZT completely reverses the proapoptotic effect of their supernatants on astrocytes, thus demonstrating that productive virus replication within M/M is required for the induction of astrocytic cell death. Taken together, data suggest that homeostasis of astrocytes may be affected by HIV-infected M/M in the absence of productive infection of target cells. This phenomenon may help to explain the cellular damage found in HIV-infected patients also in areas of the brain not strictly adjacent to HIV-infected M/M.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0741-5400
pubmed:author
pubmed:issnType
Print
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
429-35
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10985261-Anti-HIV Agents, pubmed-meshheading:10985261-Antigens, CD95, pubmed-meshheading:10985261-Apoptosis, pubmed-meshheading:10985261-Astrocytes, pubmed-meshheading:10985261-Cell Communication, pubmed-meshheading:10985261-Cells, Cultured, pubmed-meshheading:10985261-Fas Ligand Protein, pubmed-meshheading:10985261-Gene Products, tat, pubmed-meshheading:10985261-HIV, pubmed-meshheading:10985261-HIV Envelope Protein gp120, pubmed-meshheading:10985261-Homeostasis, pubmed-meshheading:10985261-Humans, pubmed-meshheading:10985261-Macrophages, pubmed-meshheading:10985261-Male, pubmed-meshheading:10985261-Membrane Glycoproteins, pubmed-meshheading:10985261-Middle Aged, pubmed-meshheading:10985261-Necrosis, pubmed-meshheading:10985261-Zidovudine, pubmed-meshheading:10985261-tat Gene Products, Human Immunodeficiency Virus
pubmed:year
2000
pubmed:articleTitle
Primary macrophages infected by human immunodeficiency virus trigger CD95-mediated apoptosis of uninfected astrocytes.
pubmed:affiliation
Department of Experimental Medicine, University of Rome Tor Vergata, Italy. aquaro@uniroma2.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't