Long-standing evidence indicates that human immunodeficiency virus type 1 (HIV-1) preferentially integrates into a subset of transcriptionally active genes of the host cell genome. However, the reason why the virus selects only certain genes among all transcriptionally active regions in a target cell remains largely unknown. Here we show that HIV-1 integration occurs in the outer shell of the nucleus in close correspondence with the nuclear pore. This region contains a series of cellular genes, which are preferentially targeted by the virus, and characterized by the presence of active transcription chromatin marks before viral infection. In contrast, the virus strongly disfavours the heterochromatic regions in the nuclear lamin-associated domains and other transcriptionally active regions located centrally in the nucleus. Functional viral integrase and the presence of the cellular Nup153 and LEDGF/p75 integration cofactors are indispensable for the peripheral integration of the virus. Once integrated at the nuclear pore, the HIV-1 DNA makes contact with various nucleoporins; this association takes part in the transcriptional regulation of the viral genome. These results indicate that nuclear topography is an essential determinant of the HIV-1 life cycle.

Nuclear architecture dictates HIV-1 integration site selection

Marini, Bruna;Lisek, Kamil;Luzzati, Roberto;Mavilio, Fulvio;Giacca, Mauro
2015

Abstract

Long-standing evidence indicates that human immunodeficiency virus type 1 (HIV-1) preferentially integrates into a subset of transcriptionally active genes of the host cell genome. However, the reason why the virus selects only certain genes among all transcriptionally active regions in a target cell remains largely unknown. Here we show that HIV-1 integration occurs in the outer shell of the nucleus in close correspondence with the nuclear pore. This region contains a series of cellular genes, which are preferentially targeted by the virus, and characterized by the presence of active transcription chromatin marks before viral infection. In contrast, the virus strongly disfavours the heterochromatic regions in the nuclear lamin-associated domains and other transcriptionally active regions located centrally in the nucleus. Functional viral integrase and the presence of the cellular Nup153 and LEDGF/p75 integration cofactors are indispensable for the peripheral integration of the virus. Once integrated at the nuclear pore, the HIV-1 DNA makes contact with various nucleoporins; this association takes part in the transcriptional regulation of the viral genome. These results indicate that nuclear topography is an essential determinant of the HIV-1 life cycle.
Pubblicato
https://www.nature.com/articles/nature14226
File in questo prodotto:
File Dimensione Formato  
Nuclear architecture dictates HIV-1 integration site selection.pdf

non disponibili

Descrizione: pdf editoriale
Tipologia: Documento in Versione Editoriale
Licenza: Digital Rights Management non definito
Dimensione 5.65 MB
Formato Adobe PDF
5.65 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
2844160_Nuclear architecture dictates HIV-1 integration site selection-PostPrint.pdf

embargo fino al 02/09/2015

Descrizione: Post Print VQR3 - This is a post-peer-review, pre-copyedit version of an article published in Nature. The final authenticated version is available online at: https://doi.org/10.1038/nature14226
Tipologia: Bozza finale post-referaggio (post-print)
Licenza: Digital Rights Management non definito
Dimensione 6.25 MB
Formato Adobe PDF
6.25 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2844160
Citazioni
  • ???jsp.display-item.citation.pmc??? 146
  • Scopus 204
  • ???jsp.display-item.citation.isi??? 198
social impact