The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation
A growing number of studies indicate that mRNAs and long ncRNAs can affect protein populations by assembling dynamic ribonucleoprotein (RNP) granules. These phase-separated molecular ‘sponges’, stabilized by quinary (transient and weak) interactions, control proteins involved in numerous biological...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/11/2312 |
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| author | Sébastien Lyonnais S. Kashif Sadiq Cristina Lorca-Oró Laure Dufau Sara Nieto-Marquez Tuixent Escribà Natalia Gabrielli Xiao Tan Mohamed Ouizougun-Oubari Josephine Okoronkwo Michèle Reboud-Ravaux José Maria Gatell Roland Marquet Jean-Christophe Paillart Andreas Meyerhans Carine Tisné Robert J. Gorelick Gilles Mirambeau |
| author_facet | Sébastien Lyonnais S. Kashif Sadiq Cristina Lorca-Oró Laure Dufau Sara Nieto-Marquez Tuixent Escribà Natalia Gabrielli Xiao Tan Mohamed Ouizougun-Oubari Josephine Okoronkwo Michèle Reboud-Ravaux José Maria Gatell Roland Marquet Jean-Christophe Paillart Andreas Meyerhans Carine Tisné Robert J. Gorelick Gilles Mirambeau |
| author_sort | Sébastien Lyonnais |
| collection | DOAJ |
| description | A growing number of studies indicate that mRNAs and long ncRNAs can affect protein populations by assembling dynamic ribonucleoprotein (RNP) granules. These phase-separated molecular ‘sponges’, stabilized by quinary (transient and weak) interactions, control proteins involved in numerous biological functions. Retroviruses such as HIV-1 form by self-assembly when their genomic RNA (gRNA) traps Gag and GagPol polyprotein precursors. Infectivity requires extracellular budding of the particle followed by maturation, an ordered processing of ∼2400 Gag and ∼120 GagPol by the viral protease (PR). This leads to a condensed gRNA-NCp7 nucleocapsid and a CAp24-self-assembled capsid surrounding the RNP. The choreography by which all of these components dynamically interact during virus maturation is one of the missing milestones to fully depict the HIV life cycle. Here, we describe how HIV-1 has evolved a dynamic RNP granule with successive weak–strong–moderate quinary NC-gRNA networks during the sequential processing of the GagNC domain. We also reveal two palindromic RNA-binding triads on NC, KxxFxxQ and QxxFxxK, that provide quinary NC-gRNA interactions. Consequently, the nucleocapsid complex appears properly aggregated for capsid reassembly and reverse transcription, mandatory processes for viral infectivity. We show that PR is sequestered within this RNP and drives its maturation/condensation within minutes, this process being most effective at the end of budding. We anticipate such findings will stimulate further investigations of quinary interactions and emergent mechanisms in crowded environments throughout the wide and growing array of RNP granules. |
| first_indexed | 2024-03-10T04:58:57Z |
| format | Article |
| id | doaj.art-35afacfa36b0410b8a99db77793c381e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T04:58:57Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-35afacfa36b0410b8a99db77793c381e2023-11-23T01:58:37ZengMDPI AGViruses1999-49152021-11-011311231210.3390/v13112312The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during MaturationSébastien Lyonnais0S. Kashif Sadiq1Cristina Lorca-Oró2Laure Dufau3Sara Nieto-Marquez4Tuixent Escribà5Natalia Gabrielli6Xiao Tan7Mohamed Ouizougun-Oubari8Josephine Okoronkwo9Michèle Reboud-Ravaux10José Maria Gatell11Roland Marquet12Jean-Christophe Paillart13Andreas Meyerhans14Carine Tisné15Robert J. Gorelick16Gilles Mirambeau17Infectious Disease & AIDS Research Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, SpainInfection Biology Laboratory, Department of Experimental and Health Sciences (DCEXS), Universitat Pompeu Fabra, Carrer Doctor Aiguader 88, 08003 Barcelona, SpainInfectious Disease & AIDS Research Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, SpainBiological Adaptation and Ageing (B2A), CNRS UMR 8256 & INSERM ERL U1164, Institut de Biologie Paris-Seine (IBPS), Faculté des Sciences et d’Ingénierie (FSI), Sorbonne Université, 7 Quai St Bernard, CEDEX 05, 75252 Paris, FranceInfectious Disease & AIDS Research Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, SpainInfectious Disease & AIDS Research Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, SpainInfectious Disease & AIDS Research Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, SpainInfectious Disease & AIDS Research Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, SpainInfectious Disease & AIDS Research Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, SpainInfectious Disease & AIDS Research Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, SpainBiological Adaptation and Ageing (B2A), CNRS UMR 8256 & INSERM ERL U1164, Institut de Biologie Paris-Seine (IBPS), Faculté des Sciences et d’Ingénierie (FSI), Sorbonne Université, 7 Quai St Bernard, CEDEX 05, 75252 Paris, FranceInfectious Disease & AIDS Research Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, SpainArchitecture et Réactivité de l’ARN, CNRS UPR 9002, Université de Strasbourg, 2 Allée Conrad Roentgen, 67000 Strasbourg, FranceArchitecture et Réactivité de l’ARN, CNRS UPR 9002, Université de Strasbourg, 2 Allée Conrad Roentgen, 67000 Strasbourg, FranceInfection Biology Laboratory, Department of Experimental and Health Sciences (DCEXS), Universitat Pompeu Fabra, Carrer Doctor Aiguader 88, 08003 Barcelona, SpainExpression Génétique Microbienne, CNRS UMR 8261, Institut de Biologie Physico-Chimique (IBPC), Université de Paris, 13 Rue Pierre et Marie Curie, 75005 Paris, FranceAIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USAInfectious Disease & AIDS Research Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, SpainA growing number of studies indicate that mRNAs and long ncRNAs can affect protein populations by assembling dynamic ribonucleoprotein (RNP) granules. These phase-separated molecular ‘sponges’, stabilized by quinary (transient and weak) interactions, control proteins involved in numerous biological functions. Retroviruses such as HIV-1 form by self-assembly when their genomic RNA (gRNA) traps Gag and GagPol polyprotein precursors. Infectivity requires extracellular budding of the particle followed by maturation, an ordered processing of ∼2400 Gag and ∼120 GagPol by the viral protease (PR). This leads to a condensed gRNA-NCp7 nucleocapsid and a CAp24-self-assembled capsid surrounding the RNP. The choreography by which all of these components dynamically interact during virus maturation is one of the missing milestones to fully depict the HIV life cycle. Here, we describe how HIV-1 has evolved a dynamic RNP granule with successive weak–strong–moderate quinary NC-gRNA networks during the sequential processing of the GagNC domain. We also reveal two palindromic RNA-binding triads on NC, KxxFxxQ and QxxFxxK, that provide quinary NC-gRNA interactions. Consequently, the nucleocapsid complex appears properly aggregated for capsid reassembly and reverse transcription, mandatory processes for viral infectivity. We show that PR is sequestered within this RNP and drives its maturation/condensation within minutes, this process being most effective at the end of budding. We anticipate such findings will stimulate further investigations of quinary interactions and emergent mechanisms in crowded environments throughout the wide and growing array of RNP granules.https://www.mdpi.com/1999-4915/13/11/2312HIV-1nucleocapsidRNAliquid–liquid phase separationproteasemolecular dynamics |
| spellingShingle | Sébastien Lyonnais S. Kashif Sadiq Cristina Lorca-Oró Laure Dufau Sara Nieto-Marquez Tuixent Escribà Natalia Gabrielli Xiao Tan Mohamed Ouizougun-Oubari Josephine Okoronkwo Michèle Reboud-Ravaux José Maria Gatell Roland Marquet Jean-Christophe Paillart Andreas Meyerhans Carine Tisné Robert J. Gorelick Gilles Mirambeau The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation Viruses HIV-1 nucleocapsid RNA liquid–liquid phase separation protease molecular dynamics |
| title | The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
| title_full | The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
| title_fullStr | The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
| title_full_unstemmed | The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
| title_short | The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation |
| title_sort | hiv 1 nucleocapsid regulates its own condensation by phase separated activity enhancing sequestration of the viral protease during maturation |
| topic | HIV-1 nucleocapsid RNA liquid–liquid phase separation protease molecular dynamics |
| url | https://www.mdpi.com/1999-4915/13/11/2312 |
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