LJC

Partenaires

CNRS

Rechercher

Sur ce site

Sur le Web du CNRS

Accueil du site > Animations Scientifiques > Séminaires 2013 > Francesca Di Nunzio - HIV-1 docking at the nuclear pore, nuclear import and integration, concerted steps of HIV-1 infection

Francesca Di Nunzio - HIV-1 docking at the nuclear pore, nuclear import and integration, concerted steps of HIV-1 infection

Speaker : Francesca Di Nunzio - Departement de Virologie - Institut Pasteur - Paris

When : thursday 31st January at 11 am

Where : Salle CO23 (grande salle de réunions du CBP rez-de-chaussée LR6)

Title : HIV-1 docking at the nuclear pore, nuclear import and integration, concerted steps of HIV-1 infection

HIV to productively infect a cell must first negotiate an uncertain pathway through the cell’s cytoplasm to arrive at the nucleus and then integrate into the host genome. Recently, we set up a new technology “FlAsH-PALM” that allowed us to visualize early steps of HIV infection. We resolved IN localization and virion morphology at 30 nm resolution and detect a substantial change in virus size between cytoplasmic and nuclear complexes. Our results suggested that at 2 h post-infection an important fraction of the cytoplasmic viral material remains encapsidated with the IN randomly distributed inside the capsid volume. We have also investigated the interaction between the nuclear pore complex (NPC) and HIV. The NPC mediates nucleo-cytoplasmic transport of macromolecules and is an obligatory point of passage and functional bottleneck in the replication of some viruses. The HIV has evolved the required mechanisms for active nuclear import of its genome through the NPC. However these mechanisms are still unknown. Recently we observed that TNPO3 is involved in a new unknown step after nuclear import but before integration. We have also investigated the involvement of key nucleoporins in HIV docking, translocation, and integration. We showed the first docking factor, RanBP2/Nup358, for HIV-1 cores at NPC. We found that Nup153 binds in vitro assembled HIV-1 CA-NC complexes as strong as the capsid binder TRIM5αrh. Distribution analysis of integration sites in Nup153-depleted human lymphocytes revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. Finally, using quantification of NPCs, we further found that NPC density is a limiting factor for HIV-1 infection in mitotic cells and in non-dividing cells. These studies have the aim to investigate the unexplored role of nuclear pore proteins in HIV-1 integration with a potential concerted mechanism between nuclear translocation and integration.

Dans la même rubrique :