HIV-1 protease and reverse transcriptase control the architecture of their nucleocapsid partner

Gilles Mirambeau*, Sébastien Lyonnais, Dominique Coulaud, Laurence Hameau, Sophie Lafosse, Josette Jeusset, Isabelle Borde, Michèle Reboud-Ravaux, Tobias Restle, Robert J. Gorelick, Eric Le Cam

*Korrespondierende/r Autor/-in für diese Arbeit
    36 Zitate (Scopus)

    Abstract

    The HIV-1 nucleocapsid is formed during protease (PR)-directed viral maturation, and is transformed into pre-integration complexes following reverse transcription in the cytoplasm of the infected cell. Here, we report a detailed transmission electron microscopy analysis of the impact of HIV-1 PR and reverse transcriptase (RT) on nucleocapsid plasticity, using in vitro reconstitutions. After binding to nucleic acids, NCp15, a proteolytic intermediate of nucleocapsid protein (NC), was processed at its C-terminus by PR, yielding premature NC (NCp9) followed by mature NC (NCp7), through the consecutive removal of p6 and p1. This allowed NC co-aggregation with its single-stranded nucleic-acid substrate. Examination of these co-aggregates for the ability of RT to catalyse reverse transcription showed an effective synthesis of double-stranded DNA that, remarkably, escaped from the aggregates more efficiently with NCp7 than with NCp9. These data offer a compelling explanation for results from previous virological studies that focused on i) Gag processing leading to nucleocapsid condensation, and ii) the disappearance of NCp7 from the HIV-1 pre-integration complexes. We propose that HIV-1 PR and RT, by controlling the nucleocapsid architecture during the steps of condensation and dismantling, engage in a successive nucleoprotein-remodelling process that spatiotemporally coordinates the pre-integration steps of HIV-1. Finally we suggest that nucleoprotein remodelling mechanisms are common features developed by mobile genetic elements to ensure successful replication.

    OriginalspracheEnglisch
    Aufsatznummere669
    ZeitschriftPLoS ONE
    Jahrgang2
    Ausgabenummer8
    DOIs
    PublikationsstatusVeröffentlicht - 22.08.2007

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