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.
- Leo C James
- Leo C James
- Till Böcking
- David A Jacques
- William A McEwan
- Gregory J Towers
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Wesley I Sundquist, University of Utah School of Medicine, United States
© 2018, Mallery et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Structural and biophysical studies help to follow the disassembly of the HIV-1 capsid in vitro, and reveal the role of a small molecule called IP6 in regulating capsid stability.
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