Chromatin organization at the nuclear pore favours HIV replication.

Mickaël Lelek (1) , Nicoletta Casartelli (2) , Danilo Pellin (3) , Ermanno Rizzi (4) , Philippe Souque (5) , Marco Severgnini (4) , Clelia Di Serio (3) , Thomas Fricke (6) , Felipe Diaz-Griffero (6) , Christophe Zimmer (1) , Pierre Charneau (5) , Francesca Di Nunzio (5)

1 Imagerie et Modélisation
2 Virus et Immunité
3 Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics
4 ITB - Institute for Biomedical Technologies
5 Virologie moléculaire et Vaccinologie
6 Albert Einstein College of Medicine [New York]

The molecular mechanisms that allow HIV to integrate into particular sites of the host genome are poorly understood. Here we tested if the nuclear pore complex (NPC) facilitates the targeting of HIV integration by acting on chromatin topology. We show that the integrity of the nuclear side of the NPC, which is mainly composed of Tpr, is not required for HIV nuclear import, but that Nup153 is essential. Depletion of Tpr markedly reduces HIV infectivity, but not the level of integration. HIV integration sites in Tpr-depleted cells are less associated with marks of active genes, consistent with the state of chromatin proximal to the NPC, as analysed by super-resolution microscopy. LEDGF/p75, which promotes viral integration into active genes, stabilizes Tpr at the nuclear periphery and vice versa. Our data support a model in which HIV nuclear import and integration are concerted steps, and where Tpr maintains a chromatin environment favourable for HIV replication.

Domains: Life Sciences [q-bio]

Mickaël Lelek, Nicoletta Casartelli, Danilo Pellin, Ermanno Rizzi, Philippe Souque, et al.. Chromatin organization at the nuclear pore favours HIV replication.. Nature Communications, 2015, 6, pp.6483. ⟨10.1038/ncomms7483⟩. ⟨pasteur-01536149⟩