View the Current Issue

Article

  • The EMBO Journal (2007) 26, 424 - 435
  • doi:10.1038/sj.emboj.7601517

Suv39H1 and HP1big gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency

Isaure du Chéné1, Euguenia Basyuk2, Yea-Lih Lin3, Robinson Triboulet1, Anna Knezevich4, Christine Chable-Bessia1, Clement Mettling3, Vincent Baillat5, Jacques Reynes5, Pierre Corbeau3, Edouard Bertrand2, Alessandro Marcello4, Stephane Emiliani6, Rosemary Kiernan1 and Monsef Benkirane1

  1. Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, UPR 1142, Montpellier, France
  2. Traffic et Assemblage des RNPs, Institut de Génétique Moléculaire, UMR 5355, Montpellier, France
  3. Lentivirus et Transfert de Gènes, Institut de Génétique Humaine, UPR 1142, Montpellier, France
  4. Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
  5. Service des Maladies Infectieuses et Tropicales Hôpital Gui de Chauliac, Institut de Génétique Moléculaire, UMR 5355, Montpellier, France
  6. Département de Maladies Infectieuses, Institut Cochin, Paris, France

Correspondence to:

Monsef Benkirane, Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, CNRS, UPR 1142, Montpellier, 141 rue la Cardonille, 34396 Montpellier Cedex 5, France. Tel.: +33 4 99 61 99 32; Fax: + 33 4 99 61 99 01; E-mail: bmonsef@igh.cnrs.fr

Received 22 June 2006; Accepted 30 November 2006

HIV-1 gene expression is the major determinant regulating the rate of virus replication and, consequently, AIDS progression. Following primary infection, most infected cells produce virus. However, a small population becomes latently infected and constitutes the viral reservoir. This stable viral reservoir seriously challenges the hope of complete viral eradication. Viewed in this context, it is critical to define the molecular mechanisms involved in the establishment of transcriptional latency and the reactivation of viral expression. We show that Suv39H1, HP1gamma and histone H3Lys9 trimethylation play a major role in chromatin-mediated repression of integrated HIV-1 gene expression. Suv39H1, HP1gamma and histone H3Lys9 trimethylation are reversibly associated with HIV-1 in a transcription-dependent manner. Finally, we show in different cellular models, including PBMCs from HIV-1-infected donors, that HIV-1 reactivation could be achieved after HP1gamma RNA interference.

  • Keywords:

    • chromatin,
    • HIV,
    • latency,
    • reactivation,
    • transcription