Human Nucleoporins Promote HIV-1 Docking at the Nuclear Pore, Nuclear Import and Integration

Francesca Di Nunzio, Anne Danckaert, Thomas Fricke, Patricio Perez, Juliette Fernandez, Emmanuelle Perret, Pascal Roux, Spencer Shorte, Pierre Charneau, Felipe Diaz-Griffero, Nathalie J. Arhel

Research output: Contribution to journalArticle

75 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere46037
JournalPLoS One
Volume7
Issue number9
DOIs
StatePublished - Sep 25 2012

Fingerprint

Nuclear Pore Complex Proteins
nucleoporins
Nuclear Pore
Cell Nucleus Active Transport
nuclear membrane
Human immunodeficiency virus 1
Viruses
imports
HIV-1
HIV
Human immunodeficiency virus
Cyclophilins
pathogenicity
nucleocytoplasmic transport
cyclophilins
Virus Diseases
Virus Replication
Cytoskeleton
HIV infections
virus replication

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Di Nunzio, F., Danckaert, A., Fricke, T., Perez, P., Fernandez, J., Perret, E., ... Arhel, N. J. (2012). Human Nucleoporins Promote HIV-1 Docking at the Nuclear Pore, Nuclear Import and Integration. PLoS One, 7(9), [e46037]. https://doi.org/10.1371/journal.pone.0046037

Human Nucleoporins Promote HIV-1 Docking at the Nuclear Pore, Nuclear Import and Integration. / Di Nunzio, Francesca; Danckaert, Anne; Fricke, Thomas; Perez, Patricio; Fernandez, Juliette; Perret, Emmanuelle; Roux, Pascal; Shorte, Spencer; Charneau, Pierre; Diaz-Griffero, Felipe; Arhel, Nathalie J.

In: PLoS One, Vol. 7, No. 9, e46037, 25.09.2012.

Research output: Contribution to journalArticle

Di Nunzio, F, Danckaert, A, Fricke, T, Perez, P, Fernandez, J, Perret, E, Roux, P, Shorte, S, Charneau, P, Diaz-Griffero, F & Arhel, NJ 2012, 'Human Nucleoporins Promote HIV-1 Docking at the Nuclear Pore, Nuclear Import and Integration', PLoS One, vol. 7, no. 9, e46037. https://doi.org/10.1371/journal.pone.0046037
Di Nunzio F, Danckaert A, Fricke T, Perez P, Fernandez J, Perret E et al. Human Nucleoporins Promote HIV-1 Docking at the Nuclear Pore, Nuclear Import and Integration. PLoS One. 2012 Sep 25;7(9). e46037. https://doi.org/10.1371/journal.pone.0046037
Di Nunzio, Francesca ; Danckaert, Anne ; Fricke, Thomas ; Perez, Patricio ; Fernandez, Juliette ; Perret, Emmanuelle ; Roux, Pascal ; Shorte, Spencer ; Charneau, Pierre ; Diaz-Griffero, Felipe ; Arhel, Nathalie J. / Human Nucleoporins Promote HIV-1 Docking at the Nuclear Pore, Nuclear Import and Integration. In: PLoS One. 2012 ; Vol. 7, No. 9.
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