Productive infection and subsequent interaction of CD4-gp120 at the cellular membrane is required for HIV-induced apoptosis of CD4+ T cells

Corbeil, Jacques; Richman, Douglas D.

doi:10.1099/0022-1317-76-3-681

Cited by 59 publications

(34 citation statements)

References 34 publications

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“…However, despite T-cell stimulatory signals triggered by HIV-1 Env, decay processes still prevent viral The observed decay of rescuable HIV-1 is partially caused by apoptosis of the infected resting CD4 ϩ T cells. While some studies reported that productive infection of CD4 ϩ T cells is required for HIV-1-induced apoptosis (10,21,39), our data showed that infected resting CD4 ϩ T cells can undergo apoptosis even when HIV-1 reverse transcription is blocked. Apoptosis was prevented if viral fusion was blocked.…”

Section: Resting Cd4mentioning

confidence: 52%

Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4 ⁺ T Cells

Zhou

Zhang

Siliciano

et al. 2005

J Virol

180

167

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In untreated human immunodeficiency virus type 1 (HIV-1) infection, most viral genomes in resting CD4؉ T cells are not integrated into host chromosomes. This unintegrated virus provides an inducible latent reservoir because cellular activation permits integration, virus gene expression, and virus production. It remains controversial whether HIV-1 is stable in this preintegration state. Here, we monitored the fate of HIV-1 in resting CD4؉ cells by using a green fluorescent protein (GFP) reporter virus carrying an X4 envelope. After virus entry into resting CD4؉ T cells, both rescuable virus gene expression, visualized with GFP, and rescuable virion production, assessed by p24 release, decayed with a half-life of 2 days. In these cells, reverse transcription goes to completion over 2 to 3 days, and 50% of the viruses that have entered undergo functional decay before reverse transcription is complete. We distinguished two distinct but closely related factors contributing to loss of rescuable virus. First, some host cells undergo virus-induced apoptosis upon viral entry, thereby reducing the amount of rescuable virus. Second, decay processes directly affecting the virus both before and after the completion of reverse transcription contribute to the loss of rescuable virus. The functional half-life of full-length, integration-competent reverse transcripts is only 1 day. We propose that rapid intracellular decay processes compete with early steps in viral replication in infected CD4 ؉ T cells. Decay processes dominate in resting CD4؉ T cells as a result of the slow kinetics of reverse transcription and blocks at subsequent steps. Therefore, the reservoir of unintegrated HIV-1 in recently infected resting CD4 ؉ T cells is highly labile.

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Section: Resting Cd4mentioning

confidence: 52%

Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4 ⁺ T Cells

Zhou

Zhang

Siliciano

et al. 2005

J Virol

180

167

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“…HIV-mediated death of productively infected CD4ϩ T cells in vitro has, however, been found to be independent of CD95/CD95L interactions (4 -6), and the possible involvement of other members of the TNF receptor family has not been explored. Several findings suggest that viral proteins encoded by HIV-1 (gp120 envelope glycoprotein, Vpr) may induce death of either infected or uninfected CD4ϩ T cells in productively infected CD4 T cell cultures (22)(23)(24)(25)(26)(27)(28).…”

mentioning

confidence: 99%

Productive HIV-1 Infection of Primary CD4+ T Cells Induces Mitochondrial Membrane Permeabilization Leading to a Caspase-independent Cell Death

Petit¹,

Arnoult²,

Lelièvre³

et al. 2002

Journal of Biological Chemistry

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“…Human immunodeficiency virus type 1 (HIV-1) infected patient evolution toward AIDS is characterized by a progressive drop in the number of CD4 ϩ T lymphocytes, and virus-induced apoptosis has been proposed as a possible mechanism of HIV pathogenicity (17,37,42). Recent studies have demonstrated that CXCR4 triggers programmed cell death upon binding to the HIV-1 envelope glycoprotein gp120 (8,9,11,26,27).…”

mentioning

confidence: 99%

Binding of Human Immunodeficiency Virus Type 1 gp120 to CXCR4 Induces Mitochondrial Transmembrane Depolarization and Cytochromec-Mediated Apoptosis Independently of Fas Signaling

Roggero

Robert-Hebmann

Harrington

et al. 2001

J Virol

110

117

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Apoptosis of CD4؉ T lymphocytes, induced by contact between human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120) and its receptors, could contribute to the cell depletion observed in HIV-infected individuals. CXCR4 appears to play an important role in gp120-induced cell death, but the mechanisms involved in this apoptotic process remain poorly understood. To get insight into the signal transduction pathways connecting CXCR4 to apoptosis following gp120 binding, we used different cell lines expressing wild-type CXCR4 and a truncated form of CD4 that binds gp120 but lacks the ability to transduce signals. The present study demonstrates that (i) the interaction of cell-associated gp120 with CXCR4-expressing target cells triggers a rapid dissipation of the mitochondrial transmembrane potential resulting in the cytosolic release of cytochrome c from the mitochondria to cytosol, concurrent with activation of caspase-9 and -3; (ii) this apoptotic process is independent of Fas signaling; and (iii) cooperation with a CD4 signal is not required. In addition, following coculture with cells expressing gp120, a Fas-independent apoptosis involving mitochondria and caspase activation is also observed in primary umbilical cord blood CD4 ؉ T lymphocytes expressing high levels of CXCR4. Thus, this gp120-mediated apoptotic pathway may contribute to CD4 ؉ T-cell depletion in AIDS.

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Productive infection and subsequent interaction of CD4-gp120 at the cellular membrane is required for HIV-induced apoptosis of CD4+ T cells

Cited by 59 publications

References 34 publications

Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4 ⁺ T Cells

Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4 ⁺ T Cells

Productive HIV-1 Infection of Primary CD4+ T Cells Induces Mitochondrial Membrane Permeabilization Leading to a Caspase-independent Cell Death

Binding of Human Immunodeficiency Virus Type 1 gp120 to CXCR4 Induces Mitochondrial Transmembrane Depolarization and Cytochromec-Mediated Apoptosis Independently of Fas Signaling

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Productive infection and subsequent interaction of CD4-gp120 at the cellular membrane is required for HIV-induced apoptosis of CD4+ T cells

Cited by 59 publications

References 34 publications

Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4 + T Cells

Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4 + T Cells

Productive HIV-1 Infection of Primary CD4+ T Cells Induces Mitochondrial Membrane Permeabilization Leading to a Caspase-independent Cell Death

Binding of Human Immunodeficiency Virus Type 1 gp120 to CXCR4 Induces Mitochondrial Transmembrane Depolarization and Cytochromec-Mediated Apoptosis Independently of Fas Signaling

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Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4 ⁺ T Cells

Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4 ⁺ T Cells