PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 1676268

Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis.

J C Ameisen·A Capron
View original source ↗Export metadata ↓

Abstract

Normal immature thymocytes respond to activation by undergoing programmed cell death (apoptosis), a physiological deletion mechanism involved in the selection of the T-cell repertoire. In this article, Jean Claude Ameisen and André Capron suggest that inappropriate induction of a form of programmed T-cell death could account for both qualitative and quantitative helper T-cell defects of HIV-infected patients. A model of AIDS pathogenesis is presented that may explain several features of HIV infection, including evolution of the disease and the development of defects in nonimmunological organs.

Explore related subjects

AIDS Dementia ComplexAcquired Immunodeficiency SyndromeCD4-Positive T-LymphocytesCell SurvivalEndodeoxyribonucleasesGene Expression RegulationHIVHIV Envelope Protein gp120Hematopoietic Stem CellsLymphocyte ActivationMitogensModels, BiologicalSignal TransductionJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J C Ameisen, A Capron. 1991. Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis.. https://doi.org/10.1016/0167-5699(91)90092-8

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Neuronal apoptotic signaling pathways probed and intervened by synthetically and modularly modified (SMM) chemokines.

As the main coreceptors for human immunodeficiency virus type 1 (HIV-1) entry, CXCR4 and CCR5 play important roles in HIV-associated dementia (HAD). HIV-1 glycoprotein gp120 contributes to HAD by causing neuronal damage and death, either directly by triggering apoptotic pathways or indirectly by stimulating glial cells to release neurotoxins. Here, to understand the mechanism of CXCR4 or CCR5 signaling in neuronal apoptosis associated with HAD, we have applied synthetically and modularly modified (SMM)-chemokine analogs derived from natural stromal cell-derived factor-1alpha or viral macrophage inflammatory protein-II as chemical probes of the mechanism(s) whereby these SMM-chemokines prevent or promote neuronal apoptosis. We show that inherently neurotoxic natural ligands of CXCR4, such as stromal cell-derived factor-1alpha or viral macrophage inflammatory protein-II, can be modified to protect neurons from apoptosis induced by CXCR4-preferring gp120(IIIB), and that the inhibition of CCR5 by antagonist SMM-chemokines, unlike neuroprotective CCR5 natural ligands, leads to neurotoxicity by activating a p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Furthermore, we discover distinct signaling pathways activated by different chemokine ligands that are either natural agonists or synthetic antagonists, thus demonstrating a chemical biology strategy of using chemically engineered inhibitors of chemokine receptors to study the signaling mechanism of neuronal apoptosis and survival.

AIDS Dementia Complex↗
PubMed2007

Evidence for BAG3 modulation of HIV-1 gene transcription.

A family of co-chaperone proteins that share the Bcl-2-associated athanogene (BAG) domain are involved in a number of cellular processes, including proliferation and apoptosis. Among these proteins, BAG3 has received increased attention due to its high levels in several disease models and ability to associate with Hsp70 and a number of other molecular partners. BAG3 expression is stimulated during cell response to stressful conditions, such as exposure to high temperature, heavy metals, and certain drugs. Here, we demonstrate that BAG3 expression is elevated upon HIV-1 infection of human lymphocytes and fetal microglial cells. Furthermore, BAG3 protein was detectable in the cytoplasm of reactive astrocytes in HIV-1-associated encephalopathy biopsies, suggesting that induction of BAG3 is part of the host cell response to viral infection. To assess the impact of BAG3 upregulation on HIV-1 gene expression, we performed transcription assays and demonstrated that BAG3 can suppress transcription of the HIV-1 long terminal repeat (LTR) in microglial cells. This activity was mapped to the kappaB motif of the HIV-1 LTR. Results from in vitro and in vivo binding assays revealed that BAG3 suppresses interaction of the p65 subunit of NF-kappaB with the kappaB DNA motif of the LTR. Results from binding and transcriptional assay identified the C-terminus of BAG3 as a potential domain involved in the observed inhibitory effect of BAG3 on p65 activity. These observations reveal a previously unrecognized cell response, that is, an increase in BAG3, elicited by HIV-1 infection, and may provide a new avenue for the suppression of HIV-1 gene expression.

AIDS Dementia Complex↗