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Chromatin control of Tat-mediated reactivation of latent HIV-1 provirus

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HAL Id: inserm-00663600

https://www.hal.inserm.fr/inserm-00663600

Submitted on 27 Jan 2012

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Chromatin control of Tat-mediated reactivation of latent

HIV-1 provirus

Guillemette Masse, Emmanuel Ségéral, Stéphane Emiliani

To cite this version:

Guillemette Masse, Emmanuel Ségéral, Stéphane Emiliani. Chromatin control of Tat-mediated

reacti-vation of latent HIV-1 provirus. Frontiers of Retrovirology: Complex retroviruses, retroelements and

their hosts, Sep 2009, Montpellier, France. pp.P56, �10.1186/1742-4690-6-S2-P56�. �inserm-00663600�

(2)

BioMed Central

Page 1 of 1 (page number not for citation purposes)

Retrovirology

Open Access

Poster presentation

Chromatin control of Tat-mediated reactivation of latent HIV-1

provirus

Guillemette X Masse*

1,2

, Emmanuel Ségéral

1,2

and Stéphane Emiliani

1,2 Address: 1Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France and 2Inserm, U567, Paris, France

* Corresponding author

Background

Human Immunodeficiency Virus (HIV-1) persists in a latent state within resting CD4+ T cells of infected patients treated with highly active retroviral therapy (HAART). This latent reservoir should be eliminated for the clear-ance of infection. In these cells, silenced replication-com-petent viruses are integrated into the host genome and can be reactivated by T-cell stimuli. The establishment of this post-integration form of latency is a multifactorial process leading to transcriptional repression. The cellular and molecular mechanisms underlying HIV-1 promoter reac-tivation from latently infected cells are still poorly under-stood.

Materials and methods

We used a Jurkat CD4+T cell model of post-integration latency (J-lat cells) to assess the role of cellular factors in controlling gene silencing and Tat-mediated reactivation of silenced HIV proviruses. Our study focused on: (1) the Tat-associated-kinase complex P-TEFb (e.g. Cyclin T1 and CDK9), stimulating progressive elongation, (2) chroma-tin remodeler SWI/SNF complexes (e.g. Brm and Brg-1), (3) and potential regulators of gene silencing as Hetero-chromatin Protein 1-γ (HP1-γ and Argonaute 1 (Ago1). Upon transient shRNA knockdowns, viral reactivation by NFkB inducers (TNFα) and/or HDAC inhibitors (TSA) was analyzed by FACS and un-spliced and multi-spliced forms of HIV-1 transcripts were quantified by RT-qPCR.

Results

Our results showed that, as expected, P-TEFb factors inhi-bition impaired transcriptional reactivation of latent

HIV-1. On the contrary, Brg-1 knockdown stimulated TNFα-induced HIV-1 expression, suggesting that the SWI/SNF complex could participate to transcriptional repression in this model. Furthermore, TNFα- and TSA-induced viral mRNA transcript abundance showed a 3 to 4 fold increase upon Ago1 knockdown.

Conclusion

HIV-1 viral clearance through reactivation would imply the regulation of cellular cofactors involved in the chro-matin control of the LTR. Our data suggest that establish-ment and reactivation of viral latency is under the control of several cellular mechanisms involving factors control-ling heterochromatin formation, as well as complexes mediating RNA silencing.

from Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts

Montpellier, France. 21-23 September 2009 Published: 24 September 2009

Retrovirology 2009, 6(Suppl 2):P56 doi:10.1186/1742-4690-6-S2-P56

<supplement> <title> <p>Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts</p> </title> <note>Meeting abstracts - A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S2-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf</url> </supplement>

This abstract is available from: http://www.retrovirology.com/content/6/S2/P56 © 2009 Masse et al; licensee BioMed Central Ltd.

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