Chromatin organization at the nuclear pore favours HIV replication.
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.
Institut Pasteur, Unité Imagerie et Modélisation, CNRS 3691, Paris 75015, France.
Mickaël
M
Lelek
Institut Pasteur, Unité Virus et Immunité Unité, CNRS 3015, Paris 75015, France.
Nicoletta
N
Casartelli
Vita-Salute San Raffaele University Centre for Statistics in the Biomedical Sciences, Milan 20132, Italy.
Danilo
D
Pellin
Institute for Biomedical Technologies (ITB), CNR, via F.lli Cervi 93, Segrate 20090, Italy.
Ermanno
0000000298982326
E
Rizzi
Institut Pasteur, Unité Virologie Moléculaire et Vaccinologie, CNRS 3569, Paris 75015, France.
Philippe
P
Souque
Institute for Biomedical Technologies (ITB), CNR, via F.lli Cervi 93, Segrate 20090, Italy.
Marco
0000000186551206
M
Severgnini
Vita-Salute San Raffaele University Centre for Statistics in the Biomedical Sciences, Milan 20132, Italy.
Clelia
C
Di Serio
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Thomas
T
Fricke
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Felipe
F
Diaz-Griffero
Institut Pasteur, Unité Imagerie et Modélisation, CNRS 3691, Paris 75015, France.
Christophe
C
Zimmer
Institut Pasteur, Unité Virologie Moléculaire et Vaccinologie, CNRS 3569, Paris 75015, France.
Pierre
P
Charneau
Institut Pasteur, Unité Virologie Moléculaire et Vaccinologie, CNRS 3569, Paris 75015, France.
Francesca
F
Di Nunzio
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D015153:Blotting, Western; D002843:Chromatin / Q000378:metabolism*; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008156:Luciferases; D018613:Microscopy, Confocal; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D016662:Virus Integration / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; C079377:NUP153 protein, human; D028861:Nuclear Pore Complex Proteins; D009841:Oligonucleotides; C504649:PSIP1 protein, human; D011518:Proto-Oncogene Proteins; C073597:TPR protein, human; D014157:Transcription Factors; D008156:Luciferases