How HIV-1 Uses the Metabolite Inositol Hexakisphosphate to Build Its Capsid
The HIV-1 capsid is one of virology’s most iconic structures, yet how it assembles has long remained elusive. Remarkably, the capsid is made from just a single protein, CA, which forms a lattice of ~250 hexamers and exactly 12 pentamers. Conical capsids form inside budded virions during maturation,...
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2025-05-01
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| author | Leo C. James |
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| description | The HIV-1 capsid is one of virology’s most iconic structures, yet how it assembles has long remained elusive. Remarkably, the capsid is made from just a single protein, CA, which forms a lattice of ~250 hexamers and exactly 12 pentamers. Conical capsids form inside budded virions during maturation, but early efforts to reproduce this in vitro resulted instead in open-ended tubes with a purely hexameric lattice. The missing component in capsid assembly was finally identified as the metabolite inositol hexakisphosphate (IP6). Simply mixing soluble CA protein with IP6 is sufficient to drive the spontaneous assembly of conical capsids with a similar size and shape to those inside of infectious virions. Equally important, IP6 stabilises capsids once formed, increasing their stability from minutes to hours. Indeed, such is the dependence of HIV-1 on IP6 that the virus actively packages it into virions during production. These discoveries have stimulated work from multiple labs into the role and importance of IP6 in HIV-1 replication, and is the subject of this review. |
| format | Article |
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| institution | OA Journals |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj-art-2c33f942d7cb42b390d01cef58461bb82025-08-20T02:34:02ZengMDPI AGViruses1999-49152025-05-0117568910.3390/v17050689How HIV-1 Uses the Metabolite Inositol Hexakisphosphate to Build Its CapsidLeo C. James0MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UKThe HIV-1 capsid is one of virology’s most iconic structures, yet how it assembles has long remained elusive. Remarkably, the capsid is made from just a single protein, CA, which forms a lattice of ~250 hexamers and exactly 12 pentamers. Conical capsids form inside budded virions during maturation, but early efforts to reproduce this in vitro resulted instead in open-ended tubes with a purely hexameric lattice. The missing component in capsid assembly was finally identified as the metabolite inositol hexakisphosphate (IP6). Simply mixing soluble CA protein with IP6 is sufficient to drive the spontaneous assembly of conical capsids with a similar size and shape to those inside of infectious virions. Equally important, IP6 stabilises capsids once formed, increasing their stability from minutes to hours. Indeed, such is the dependence of HIV-1 on IP6 that the virus actively packages it into virions during production. These discoveries have stimulated work from multiple labs into the role and importance of IP6 in HIV-1 replication, and is the subject of this review.https://www.mdpi.com/1999-4915/17/5/689HIV-1IP6retrovirusescapsidstructurevirus replication |
| spellingShingle | Leo C. James How HIV-1 Uses the Metabolite Inositol Hexakisphosphate to Build Its Capsid Viruses HIV-1 IP6 retroviruses capsid structure virus replication |
| title | How HIV-1 Uses the Metabolite Inositol Hexakisphosphate to Build Its Capsid |
| title_full | How HIV-1 Uses the Metabolite Inositol Hexakisphosphate to Build Its Capsid |
| title_fullStr | How HIV-1 Uses the Metabolite Inositol Hexakisphosphate to Build Its Capsid |
| title_full_unstemmed | How HIV-1 Uses the Metabolite Inositol Hexakisphosphate to Build Its Capsid |
| title_short | How HIV-1 Uses the Metabolite Inositol Hexakisphosphate to Build Its Capsid |
| title_sort | how hiv 1 uses the metabolite inositol hexakisphosphate to build its capsid |
| topic | HIV-1 IP6 retroviruses capsid structure virus replication |
| url | https://www.mdpi.com/1999-4915/17/5/689 |
| work_keys_str_mv | AT leocjames howhiv1usesthemetaboliteinositolhexakisphosphatetobuilditscapsid |