Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)

Barré‐Sinoussi, Françoise; Chermann, Jean‐Claude; fa, r e ff d eba b b b eb; Nugeyre, Marie-Thérèse; Chamaret, S.; Gruest, J; Dauguet, C.; Axler-Blin, C.; Vézinet-Brun, F.; Rouzioux, C.; Rozenbaum, Willy; Montagnier, Luc

doi:10.1126/science.6189183

Cited by 5,953 publications

(2,292 citation statements)

References 8 publications

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“…The HIV protease is a virus-encoded enzyme absolutely required for virus propagation and infectivity. In the HIV infected cell, unspliced genomic RNA serves as mRNA for the synthesis of Gag and Gag-Pol polyproteins [1,2]. As part of the Gag-Pol polyprotein, the HIV protease is flanked at the N-terminus by a transframe region (TFR) and at the C-terminus by the reverse transcriptase [3,4].…”

Section: Introductionmentioning

confidence: 99%

Autoprocessing of human immunodeficiency virus type 1 protease miniprecursor fusions in mammalian cells

Huang

Chen

2010

AIDS Res Ther

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BackgroundHIV protease (PR) is a virus-encoded aspartic protease that is essential for viral replication and infectivity. The fully active and mature dimeric protease is released from the Gag-Pol polyprotein as a result of precursor autoprocessing.ResultsWe here describe a simple model system to directly examine HIV protease autoprocessing in transfected mammalian cells. A fusion precursor was engineered encoding GST fused to a well-characterized miniprecursor, consisting of the mature protease along with its upstream transframe region (TFR), and small peptide epitopes to facilitate detection of the precursor substrate and autoprocessing products. In HEK 293T cells, the resulting chimeric precursor undergoes effective autoprocessing, producing mature protease that is rapidly degraded likely via autoproteolysis. The known protease inhibitors Darunavir and Indinavir suppressed both precursor autoprocessing and autoproteolysis in a dose-dependent manner. Protease mutations that inhibit Gag processing as characterized using proviruses also reduced autoprocessing efficiency when they were introduced to the fusion precursor. Interestingly, autoprocessing of the fusion precursor requires neither the full proteolytic activity nor the majority of the N-terminal TFR region.ConclusionsWe suggest that the fusion precursors provide a useful system to study protease autoprocessing in mammalian cells, and may be further developed for screening of new drugs targeting HIV protease autoprocessing.

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Section: Introductionmentioning

confidence: 99%

Autoprocessing of human immunodeficiency virus type 1 protease miniprecursor fusions in mammalian cells

Huang

Chen

2010

AIDS Res Ther

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“…The human immunode®ciency virus (HIV), the agent etiologically related to the acquired immunode®ciency syndrome (AIDS) (Barre-Sinoussi et al, 1983), preferentially infects helper inducer T lymphocytes (Dalgleish et al, 1984). Termination of the long latency of AIDS in patients infected with HIV-1 is marked by a profound depletion of CD4 + T cells and the decline of HIV-1 speci®c cytotoxic CD8 + T cells (Meyaard et al, 1992(Meyaard et al, ,1994.…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Macho¹,

Calzado²,

Jiménez‐Reina³

et al. 1999

Oncogene

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The e ects of HIV-1 Tat protein on mitochondria membrane permeability and apoptosis were analysed in lymphoid cells. In this report we show that stabletransfected HIV-Tat cells are primed to undergo apoptosis upon serum withdrawal. This e ect was observed in both the Jhan T cell line and the K562 cells, the latter expressing the bcr-abl chimeric gene, which confers resistance to apoptosis induced by di erent stimuli. Using a cyto¯uorimetric approach we have determined that serum withdrawal induces a disruption of the transmembrane mitochondrial potential (Dc m ) followed by an increase of reactive oxygen species (ROS) and the subsequent DNA nuclear loss in K562-Tat cells but not in the K562-pcDNA cell line. These pre-apoptotic events were associated with the cleavage of the caspase-3, while the expression of Bcl-2, Bcl-X L and Bax proteins was not a ected by the presence of Tat. Regardless of the steady state of the Bax protein, we found that in both K562 and K562-Tat cells, this protein is located in the nucleus, but after serum withdrawal its localization was mainly in the cytoplasm. The activity of caspase-3 detected in K562-Tat cells after serum withdrawal paralleled with the mitochondria permeability transition. Nevertheless, in Jhan-Tat cells the inhibition of this caspase with the speci®c inhibitor, z-DEVD-cmk, did not a ect the disruption of the mitochondria potential induced by serum withdrawal. Interestingly, we found that HIV-Tat protein accumulates at the mitochondria in the K562-Tat cells cultured under low serum conditions, and this mitochondrial localization correlated with the Dc m disruption detected in these cells. In addition, HIV-1 Tat protein synergies with protoporphyrin IX (PPIX), a ligand of the mitochondrial benzodiazepine receptor, in the induction of apoptosis in both Jhan and K562 cells. Thus, HIV-1 Tat protein may induce apoptosis by a mechanism that involves mitochondrial PT and may contribute to the lymphocyte depletion seen in AIDS patients.

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“…Professeur Jean-François Delfraissy Éditorial > L'année 2013 marque le 30 e anniversaire de la découverte du VIH-1 (virus de l'immunodéficience humaine) à l'Institut Pasteur [1]. Malgré trois décennies de lutte contre le sida et d'avancées scientifiques, les données épidémiologiques nous rappellent que l'épidémie de sida est loin d'être maîtrisée, au Nord et au Sud, et que nous devons encore nous engager et nous mobiliser dans une réponse scientifique, communautaire et associative pour aller vers un monde sans VIH.…”

Section: Quels Enjeux De Recherche Trente Ans Après L'identificationunclassified

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Delfraissy

2013

Med Sci (Paris)

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Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)

Cited by 5,953 publications

References 8 publications

Autoprocessing of human immunodeficiency virus type 1 protease miniprecursor fusions in mammalian cells

Autoprocessing of human immunodeficiency virus type 1 protease miniprecursor fusions in mammalian cells

Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis. Biochemical mechanisms

Quels enjeux de recherche trente ans après l’identification du virus VIH ?

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