Suv39H1 and HP1[gamma] are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency

• Published in: The EMBO journal 2007-01, Vol.26 (2), p.424-435
• Main Authors: Isaure du Chéné, Basyuk, Euguenia, Lin, Yea-Lih, Robinson Triboulet, Knezevich, Anna, Chable-Bessia, Christine, Mettling, Clement, Baillat, Vincent, Reynes, Jacques, Corbeau, Pierre, Bertrand, Edouard, Marcello, Alessandro, Emiliani, Stephane, Kiernan, Rosemary
• Format: Article
• Language: English
• Subjects: Chromatin; Gene expression; HIV; Human immunodeficiency virus; Human immunodeficiency virus 1
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7601517

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.