Retroviral Factors Promoting Infectivity

Cuccurullo, Emilia Cristiana; Valentini, Chiara; Pizzato, Massimo

doi:10.1016/bs.pmbts.2014.10.008

Cited by 2 publications

(2 citation statements)

References 239 publications

(206 reference statements)

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“…While both mature during GagPol processing, IN has been shown recently to be a key actor in properly coordinating RNP granular condensation and capsid reassembly within the viral particle 61,62 . These dynamics also offer new schemes to revisit the proposed implications of HIV-1 Nef, Vif, Tat and Vpr auxiliary proteins within the design of an infectious particle 63 . It strongly argues finally for tight control of GagPol incorporation and PR auto-processing supported by the NC domain in GagPol during particle formation 64,65 : this domain should help to position GagPol in the Gag assembly facilitating the processed PR directed by the gRNA to digest the Gag-domains NC, SP2, p6.…”

Section: Resultsmentioning

confidence: 99%

The HIV-1 ribonucleoprotein dynamically regulates its condensate behavior and drives acceleration of protease activity through membraneless granular phase separation

Lyonnais

Sadiq

Lorca-Oró

et al. 2019

Preprint

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A growing number of studies indicate that mRNAs and long ncRNAs can affect protein populations by assembling dynamic ribonucleoprotein (RNP) granules. These phaseseparated 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 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.

show abstract

Section: Resultsmentioning

confidence: 99%

The HIV-1 ribonucleoprotein dynamically regulates its condensate behavior and drives acceleration of protease activity through membraneless granular phase separation

Lyonnais

Sadiq

Lorca-Oró

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…While both mature during GagPol processing, IN has been shown recently to be a key actor in properly coordinating RNP granular condensation and capsid reassembly within the viral particle [121][122][123]. These dynamics also offer new schemes to revisit the proposed implications of HIV-1 Nef, Vif, Tat, and Vpr auxiliary proteins within the design of an infectious particle [124]. Our findings suggest tight temporal control of GagPol incorporation and PR auto-processing supported by the NC domain in GagPol during particle formation [125,126]: this domain should help to position GagPol in the Gag assembly, facilitating the processed PR directed by the gRNA to digest the Gag-domains NC, SP2, and p6.…”

Section: Discussionmentioning

confidence: 99%

The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation

Lyonnais

Sadiq

Lorca-Oró

et al. 2021

Viruses

View full text Add to dashboard Cite

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.

show abstract

Retroviral Factors Promoting Infectivity

Cited by 2 publications

References 239 publications

The HIV-1 ribonucleoprotein dynamically regulates its condensate behavior and drives acceleration of protease activity through membraneless granular phase separation

The HIV-1 ribonucleoprotein dynamically regulates its condensate behavior and drives acceleration of protease activity through membraneless granular phase separation

The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation

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