Nup153 Unlocks the Nuclear Pore Complex for HIV-1 Nuclear Translocation in Nondividing Cells

Journal of Virology
Cindy BuffoneFelipe Diaz-Griffero

Abstract

Human immunodeficiency virus type 1 (HIV-1) displays the unique ability to infect nondividing cells. The capsid of HIV-1 is the viral determinant for viral nuclear import. To understand the cellular factors involved in the ability of HIV-1 to infect nondividing cells, we sought to find capsid mutations that allow the virus to infect dividing but not nondividing cells. Because the interaction of capsid with the nucleoporin protein 153 (Nup153) is important for nuclear import of HIV-1, we solved new crystal structures of hexameric HIV-1 capsid in complex with a Nup153-derived peptide containing a phenylalanine-glycine repeat (FG repeat), which we used to guide structure-based mutagenesis of the capsid-binding interface. HIV-1 viruses with mutations in these capsid residues were tested for their ability to infect dividing and nondividing cells. HIV-1 viruses with capsid N57 substitutions infected dividing but not nondividing cells. Interestingly, HIV-1 viruses with N57 mutations underwent reverse transcription but not nuclear translocation. The mutant capsids also lost the ability to interact with Nup153 and CPSF6. The use of small molecules PF74 and BI-2 prevented the interaction of FG-containing nucleoporins (Nups), such as Nup1...Continue Reading

References

Apr 1, 1989·Genes & Development·B BowermanH E Varmus
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·M I BukrinskyM Stevenson
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·P GallayD Trono
Oct 6, 1998·Annual Review of Biochemistry·I W Mattaj, L Englmeier
Jan 5, 1999·Science·B K GanserW I Sundquist
Apr 15, 1999·The EMBO Journal·S NakielnyG Dreyfuss
May 1, 2001·Nature Medicine·S L ButlerF D Bushman
Jul 11, 2003·The EMBO Journal·Ariberto FassatiJosé-Manuel Mingot
Feb 14, 2004·Journal of Virology·Barbie K Ganser-PornillosWesley I Sundquist
May 14, 2004·Journal of Virology·Masahiro Yamashita, Michael Emerman
Aug 18, 2004·PLoS Biology·Rick S MitchellFrederic D Bushman
Feb 25, 2005·Bioinformatics·Thomas D Wu, Colin K Watanabe
Nov 29, 2005·Nature Medicine·Angela CiuffiFrederic Bushman
Dec 21, 2005·Virology·Masahiro Yamashita, Michael Emerman
Oct 28, 2006·Retrovirology·Ariberto Fassati
Feb 17, 2007·Nature Reviews. Microbiology·Youichi Suzuki, Robert Craigie
Mar 6, 2007·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·E K ParkK S Kim
Apr 24, 2007·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jan De RijckZeger Debyser
Oct 31, 2007·PLoS Pathogens·Masahiro YamashitaMichael Emerman
Aug 30, 2008·Current Biology : CB·Frauke ChristZeger Debyser
Nov 4, 2008·Cell Host & Microbe·Honglin ZhouAmy S Espeseth
Feb 6, 2009·Retrovirology·Lyubov ZaitsevaAriberto Fassati
Mar 5, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gary P WangFrederic D Bushman
Mar 17, 2010·Cell Host & Microbe·KyeongEun LeeVineet N KewalRamani
Feb 1, 2011·Retrovirology·Wannes ThysZeger Debyser

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Citations

Mar 1, 2019·Journal of Virology·Douglas K FischerZandrea Ambrose
Jul 18, 2019·Nature Reviews. Microbiology·Barbie K Ganser-Pornillos, Owen Pornillos
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alžběta DostálkováMichaela Rumlová
Apr 28, 2019·Virologica Sinica·Mariia NovikovaKe Peng
Nov 2, 2019·Diseases·Carole McArthurKamal Singh
Apr 23, 2020·Viruses·Sanjeev Kumar V VernekarZhengqiang Wang
Dec 4, 2020·The EMBO Journal·Elena RensenFrancesca Di Nunzio
Dec 19, 2020·Nucleic Acids Research·Gregory J Bedwell, Alan N Engelman
Jan 23, 2021·Viruses·Alan N Engelman
Feb 10, 2021·Viruses·Morganne Wilbourne, Peijun Zhang
Sep 11, 2020·Journal of Virology·Augustin Penda TwizerimanaCarsten Münk
Feb 13, 2021·Viruses·Soumajit MukherjeeHalina Anton
Feb 14, 2021·Viruses·Viviana Scoca, Francesca Di Nunzio
May 1, 2021·Viruses·Luis Adrián De Jesús-GonzálezRosa María Del Ángel
Apr 20, 2021·Frontiers in Microbiology·Elenia ToccafondiMatteo Negroni
Jun 1, 2021·Frontiers in Molecular Biosciences·Kristine E YoderRoss C Larue
Jul 3, 2021·Viruses·Guillermo Blanco-Rodriguez, Francesca Di Nunzio
Mar 24, 2021·Cold Spring Harbor Perspectives in Biology·Bojana LucicMarina Lusic
Mar 25, 2021·Journal of Molecular Cell Biology·Viviana Scoca, Francesca Di Nunzio
Aug 29, 2021·Viruses·Valentina Poletti, Fulvio Mavilio

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