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.
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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.
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