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dc.contributor.authorMallery, Donna L
dc.contributor.authorMárquez, Chantal L
dc.contributor.authorMcEwan, William
dc.contributor.authorDickson, Claire F
dc.contributor.authorJacques, David A
dc.contributor.authorAnandapadamanaban, Madhanagopal
dc.contributor.authorBichel, Katsiaryna
dc.contributor.authorTowers, Gregory J
dc.contributor.authorSaiardi, Adolfo
dc.contributor.authorBöcking, Till
dc.contributor.authorJames, Leo C
dc.date.accessioned2018-10-03T04:43:46Z
dc.date.available2018-10-03T04:43:46Z
dc.date.issued2018-05-31
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283034
dc.description.abstractThe 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.
dc.format.mediumElectronic
dc.languageeng
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectHIV-1
dc.subjectVirion
dc.subjectCapsid
dc.subjectPolymers
dc.subjectSubtilisin
dc.subjectNucleotides
dc.subjectDNA, Viral
dc.subjectAdenosine Triphosphate
dc.subjectReverse Transcriptase Inhibitors
dc.subjectVirus Assembly
dc.subjectReverse Transcription
dc.subjectHEK293 Cells
dc.titleIP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis.
dc.typeArticle
prism.publicationDate2018
prism.publicationNameElife
prism.volume7
dc.identifier.doi10.17863/CAM.30397
dcterms.dateAccepted2018-05-29
rioxxterms.versionofrecord10.7554/eLife.35335
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-05-31
dc.contributor.orcidMcEwan, William [0000-0002-4408-0407]
dc.contributor.orcidJacques, David A [0000-0002-6426-4510]
dc.contributor.orcidBöcking, Till [0000-0003-1165-3122]
dc.contributor.orcidJames, Leo C [0000-0003-2131-0334]
dc.identifier.eissn2050-084X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (206248/Z/17/Z)
cam.issuedOnline2018-05-31


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International