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

DOI: 10.7554/eLife.35335 DOI Help

Authors: Donna L. Mallery (Medical Research Council Laboratory of Molecular Biology) , Chantal L. Márquez (University of New South Wales) , William A. Mcewan (Medical Research Council Laboratory of Molecular Biology) , Claire Dickson (Medical Research Council Laboratory of Molecular Biology) , David A. Jacques (University of New South Wales) , Madhanagopal Anandapadamanaban (Medical Research Council Laboratory of Molecular Biology) , Katsia Bichel (University College London) , Gregory J. Towers (University College London) , Adolfo Saiardi (Medical Research Council (MRC) Laboratory for Molecular Cell Biology, University College London) , Till Böcking (University of New South Wales) , Leo C. James (Medical Research Council Laboratory of Molecular Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 7

State: Published (Approved)
Published: May 2018

Open Access Open Access

Abstract: The HIV capsid is semi-permeable 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.

Journal Keywords: HIV-1; IP6; capsid; co-factor; reverse transcription

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography

Documents:
elife-35335-v1.pdf