Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration.

Abstract : The nuclear pore complex (NPC) mediates nucleo-cytoplasmic transport of macromolecules and is an obligatory point of passage and functional bottleneck in the replication of some viruses. The Human Immunodeficiency Virus (HIV) has evolved the required mechanisms for active nuclear import of its genome through the NPC. However the mechanisms by which the NPC allows or even assists HIV translocation are still unknown. We investigated the involvement of four key nucleoporins in HIV-1 docking, translocation, and integration: Nup358/RanBP2, Nup214/CAN, Nup98 and Nup153. Although all induce defects in infectivity when depleted, only Nup153 actually showed any evidence of participating in HIV-1 translocation through the nuclear pore. We show that Nup358/RanBP2 mediates docking of HIV-1 cores on NPC cytoplasmic filaments by interacting with the cores and that the C-terminus of Nup358/RanBP2 comprising a cyclophilin-homology domain contributes to binding. We also show that Nup214/CAN and Nup98 play no role in HIV-1 nuclear import per se: Nup214/CAN plays an indirect role in infectivity read-outs through its effect on mRNA export, while the reduction of expression of Nup98 shows a slight reduction in proviral integration. Our work shows the involvement of nucleoporins in diverse and functionally separable steps of HIV infection and nuclear import.
Document type :
Journal articles
Complete list of metadatas

Cited literature [80 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-01536163
Contributor : Francesca Di Nunzio <>
Submitted on : Saturday, June 10, 2017 - 3:29:27 PM
Last modification on : Tuesday, May 21, 2019 - 2:48:53 PM
Long-term archiving on : Wednesday, December 13, 2017 - 11:36:30 AM

File

journal.pone.0046037.PDF
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Francesca Di Nunzio, Anne Danckaert, Thomas Fricke, Patricio Perez, Juliette Fernandez, et al.. Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration.. PLoS ONE, Public Library of Science, 2012, 7 (9), pp.e46037. ⟨10.1371/journal.pone.0046037⟩. ⟨pasteur-01536163⟩

Share

Metrics

Record views

61

Files downloads

237