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

Mallery, DL; Márquez, CL; McEwan, WA; Dickson, C; Jacques, DA; Anandapadamanaban, M; Bichel, K; ... James, LC; + view all (2018) IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis. eLIFE , 7 , Article e35335. 10.7554/eLife.35335. Green open access

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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.

Type: Article
Title: IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.35335
Publisher version: http://dx.doi.org/10.7554/eLife.35335
Language: English
Additional information: © 2018, Mallery et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: HIV-1, capsid, co-factor, reverse transcription
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10051322
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