IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis.

ELife
Donna L MalleryLeo C James

Abstract

The HIV capsid is semipermeable and covered in electropositive pores that are essential for viral DNA synthesis and infection. Here, we show that these pores bind the abundant cellular polyanion IP6, transforming viral stability from minutes to hours and allowing newly synthesised DNA to accumulate inside the capsid. An arginine ring within the pore coordinates IP6, which strengthens capsid hexamers by almost 10°C. Single molecule measurements demonstrate that this renders native HIV capsids highly stable and protected from spontaneous collapse. Moreover, encapsidated reverse transcription assays reveal that, once stabilised by IP6, the accumulation of new viral DNA inside the capsid increases >100 fold. Remarkably, isotopic labelling of inositol in virus-producing cells reveals that HIV selectively packages over 300 IP6 molecules per infectious virion. We propose that HIV recruits IP6 to regulate capsid stability and uncoating, analogous to picornavirus pocket factors. HIV-1/IP6/capsid/co-factor/reverse transcription.

References

Sep 27, 1985·Science·J M HogleD J Filman
May 1, 2001·Nature Medicine·S L ButlerF D Bushman
Aug 30, 2001·Proceedings of the National Academy of Sciences of the United States of America·S CampbellA Rein
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Oct 14, 2004·Journal of Virology·Véronique ZennouPaul D Bieniasz
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Mar 17, 2006·Proceedings of the National Academy of Sciences of the United States of America·Matthew StremlauJoseph Sodroski
Dec 14, 2006·Acta Crystallographica. Section D, Biological Crystallography·Airlie J McCoy
Apr 5, 2007·Nature Protocols·Cristina Azevedo, Adolfo Saiardi
Oct 25, 2007·Retrovirology·David WarrilowDavid Harrich
Jul 6, 2010·Journal of Molecular Biology·Owen PornillosMark Yeager
Nov 23, 2011·Journal of Visualized Experiments : JoVE·Vaibhav B Shah, Christopher Aiken
Jun 12, 2012·PLoS Pathogens·Anupriya AggarwalStuart G Turville
Jun 26, 2013·Acta Crystallographica. Section D, Biological Crystallography·Philip R Evans, Garib N Murshudov
Sep 19, 2014·Journal of Virology·Zana LukicEdward M Campbell
Mar 4, 2015·Nature·Bruna MariniMarina Lusic
Jul 22, 2015·Journal of Biomolecular NMR·Vincent B ChenJohn L Markley
Feb 10, 2016·Proceedings of the National Academy of Sciences of the United States of America·Gregory A SowdAlan N Engelman
Apr 26, 2016·Nature Communications·Peter J WatsonJohn W R Schwabe
Jul 16, 2016·ELife·Jonathan M WagnerOwen Pornillos
Apr 7, 2017·Journal of Virology·Sanela RankovicItay Rousso

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Citations

Jun 7, 2019·Journal of Virology·Mohammad Adnan SiddiquiMasahiro Yamashita
Jul 18, 2019·Nature Reviews. Microbiology·Barbie K Ganser-Pornillos, Owen Pornillos
Dec 7, 2019·Science Advances·Katarzyna A SkorupkaBarbie K Ganser-Pornillos
Dec 6, 2019·Journal of Virology·Iga KucharskaOwen Pornillos
Aug 4, 2019·Journal of Virology·Ayna AlfadhliEric Barklis
Nov 18, 2018·Viruses·Robert A DickLeo C James
Aug 5, 2020·Nature Structural & Molecular Biology·Tao NiPeijun Zhang
Aug 1, 2018·ELife·Martin Obr, Hans-Georg Kräusslich
Oct 16, 2019·Nature Microbiology·Juliette FernandezNathalie J Arhel
Apr 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alžběta DostálkováMichaela Rumlová
Aug 30, 2020·Viruses·Alex B Kleinpeter, Eric O Freed
Oct 2, 2019·The Journal of Biological Chemistry·Huaying ZhaoPeter Schuck
Apr 28, 2019·Virologica Sinica·Mariia NovikovaKe Peng
Nov 21, 2019·Scientific Reports·Alžběta DostálkováMichaela Rumlová
Nov 23, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yann DesfougèresAdolfo Saiardi
May 22, 2020·International Journal of Bipolar Disorders·Andrea MurruUNKNOWN International Group for The Study of Lithium Treated Patients (IGSLi)
Sep 15, 2020·Seminars in Cell & Developmental Biology·Kate DickerAlfredo Castello
Jan 23, 2021·Viruses·Alan N Engelman
Nov 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tania Maffucci, Marco Falasca
Feb 10, 2021·Viruses·Morganne Wilbourne, Peijun Zhang
Feb 18, 2021·Analytical Chemistry·Derrick LauDavid A Jacques
Feb 14, 2021·Viruses·Viviana Scoca, Francesca Di Nunzio
Jul 5, 2019·Bio-protocol·Chantal L MárquezTill Böcking
Mar 12, 2021·Science Advances·Donna L MalleryLeo C James
Jun 12, 2019·Current Opinion in Virology·Owen Pornillos, Barbie K Ganser-Pornillos
Mar 16, 2021·Cellular Microbiology·Sophie LevJulianne Teresa Djordjevic
Aug 14, 2020·Cell Chemical Biology·David FurkertDorothea Fiedler
Apr 18, 2021·Communications Biology·Luiza MendonçaPeijun Zhang

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Methods Mentioned

BETA
electron microscopy
Fluorescence
ELISA
PCR
transfection
size exclusion chromatography
fluorescence microscopy

Software Mentioned

REFMAC5
AIMLESS
CCP4
PyMOL Molecular Graphics System
COOT
Schrödinger
PHASER
iMOSFLM
MOLPROBITY
MATLAB

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