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Elife. 2018 May 31;7. pii: e35335. doi: 10.7554/eLife.35335.

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

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Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
EMBL Australia Node, Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, Australia.
ARC Centre of Excellence in Advanced Molecular Imaging, School of Medical Sciences, University of New South Wales, Sydney, Australia.
Division of Infection and Immunity, University College London, London, United Kingdom.
Medical Research Council Laboratory for Molecular Cell Biology, University College London, London, United Kingdom.


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.


HIV; IP6; capsid; human; infectious disease; microbiology; molecular biophysics; structural biology

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