HIV-1 Expression Induced by Anticancer Agents in Latently HIV-1-Infected ACH2 Cells

O'Brien, Mary C.; Ueno, Takamasa; Jahan, Nazma; Zajac-Kaye, Maria; Mitsuya, Hideo

doi:10.1006/bbrc.1995.1271

Cited by 22 publications

(18 citation statements)

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“…Several results indicate that HIV-1 is responsible for an increased overall genomic methylation. In particular, the promoters of IFN-γ, tumor suppressor p16 INK4.A gene, O 6 -methylguanine-DNA methyltransferase, and the LTR promoter of HIV-1 itself can be downregulated by methylation (26,(29)(30)(31)(32)(33). Our findings are in keeping with this general context.…”

Section: Discussionsupporting

confidence: 87%

Epigenetic reprogramming of UDP‐N‐acetylglucosamine 2‐ epimerase/N‐acetylmannosamine kinase (GNE) in HIV‐1‐ infected CEM T cells

et al. 2004

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Sialylated glycoconjugates mediate several key lymphocyte functions. We previously reported that hyposialylation occurred in latently HIV-1-infected CEM T cells, despite the fully preserved catalytic activity of several sialyltransferases. We show now that these cells are affected by a down-regulation of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), which leads to a dramatic decrease in the synthesis of CMP-sialic acid, the donor substrate of all sialyltransferases. The GNE gene promoter was found to be located in a CpG island with several regulatory motifs CREB, SP1, and AP-2. De novo hypermethylation of this promoter was observed in HIV-1-infected CEM cells. This phenomenon might explain some immunological disorders that persist in infected individuals despite long-term therapeutically controlled viral replication. Indeed, an overall decrease in sialic acid engraftment can affect glycoproteins, notably those in which the sialylation status is crucial to ensure homing, recirculation, and survival of lymphocytes.

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Section: Discussionsupporting

confidence: 87%

Epigenetic reprogramming of UDP‐N‐acetylglucosamine 2‐ epimerase/N‐acetylmannosamine kinase (GNE) in HIV‐1‐ infected CEM T cells

et al. 2004

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“…DNA methylation probably acts by impairing the binding of several important transcription factors to the 5'LTR, such as NF-κB, USF and Sp1 [290]. Various anticancer agents including 5-aza-2'deoxycytidine (5-Aza-CdR), an FDA-approved inhibitor of DNA methylation used in humans to treat myelodysplastic syndrome (marketed as Decitabine) [293], were shown to induce HIV-1 transcription in latently-infected cell lines [294] and in a doxycycline-dependent HIV-rtTA variant [99]. However the role of DNA methylation in HIV-1 latency was still controversial, and some laboratories even reported that CpG methylation did not correlate with transcriptional silencing [295].…”

Section: Dna Methylation In Hiv-1 Latency: An Area Of Enhanced Interestmentioning

confidence: 99%

Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

2009

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The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway.

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“…At the functional level, CpG methylation of the HIV-1 promoter inhibits transcription of in vitro-methylated plasmids transfected into cells (3,23,40), and it was suggested as a mechanism to maintain HIV-1 latency in long-term infected U937 cells (44). Demethylation of the HIV-1 promoter occurred in the presence of a DNA methylation inhibitor, 5-azacytidine, concomitantly with activation of the latent provirus in ACH-2 cells (35). Two mechanisms have been proposed to explain how methylation attenuates expression of the HIV-1 genome.…”

mentioning

confidence: 99%

Transcriptional Suppression of In Vitro-Integrated Human Immunodeficiency Virus Type 1 Does Not Correlate with Proviral DNA Methylation

Pion

Jordan

Biancotto

et al. 2003

J Virol

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HIV-1 Expression Induced by Anticancer Agents in Latently HIV-1-Infected ACH2 Cells

Cited by 22 publications

References 0 publications

Epigenetic reprogramming of UDP‐N‐acetylglucosamine 2‐ epimerase/N‐acetylmannosamine kinase (GNE) in HIV‐1‐ infected CEM T cells

Epigenetic reprogramming of UDP‐N‐acetylglucosamine 2‐ epimerase/N‐acetylmannosamine kinase (GNE) in HIV‐1‐ infected CEM T cells

Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

Transcriptional Suppression of In Vitro-Integrated Human Immunodeficiency Virus Type 1 Does Not Correlate with Proviral DNA Methylation

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