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Genetic Flexibility of the NKNK Motif in HIV-1 Integrases Allows Its Involvement in Multiple Functions During Infection

46 Pages Posted: 10 Jul 2018 Sneak Peek Status: Review Complete

See all articles by Marine Kanja

Marine Kanja

University of Strasbourg - Architecture et Réactivité de l’ARN

Pierre Cappy

University of Strasbourg - Architecture et Réactivité de l’ARN

Guillermo Blanco-Rodriguez

University of Paris-Saclay - Molecular Virology and Vaccinology Unit (VMV)

Nicolas Levy

University of Strasbourg - Chromatin Stability and DNA mobility

Oyndamola Oladosu

University of Strasbourg - Chromatin Stability and DNA mobility

Sylvie Schmidt

University of Strasbourg - Molecular Immuno-Rhumatology Laboratory

Romain Gasser

University of Strasbourg - Architecture et Réactivité de l’ARN

Paola Rossolillo

University of Strasbourg - Architecture et Réactivité de l’ARN

Christiane Moog

University of Strasbourg - Molecular Immuno-Rhumatology Laboratory

Marc Ruff

University of Strasbourg - Chromatin Stability and DNA mobility

Francesca Di Nunzio

University of Paris-Saclay - Molecular Virology and Vaccinology Unit (VMV)

Matteo Negroni

University of Strasbourg - Architecture et Réactivité de l’ARN

Daniela Lener

University of Strasbourg - Architecture et Réactivité de l’ARN

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Abstract

Generating chimerical integrases between isolates of the HIV-1 group responsible for the AIDS pandemic (group M) and of the minor group O, we identify a new functional motif, in the C-terminal domain of integrases M, constituted of two lysines and two asparagines (NKNK). Removing these residues abolishes catalysis in vitro and the generation of proviral DNA in tissue culture. A decrease of reverse transcription and nuclear import of reverse transcription products is also observed. Remarkably, the motif shows a potential genetic flexibility with respect to integration. Indeed, despite its strict conservation in vivo, the positions of the residues in the motif can be permutated retaining in most cases the ability to generate proviral DNA. Reverse transcription is instead optimal exclusively with the canonical NKNK motif. The versatility of this region regarding integration could therefore have provided a major asset for this enzyme to acquire additional functions in the infectious cycle.

Note: Comments welcome.

Suggested Citation

Kanja, Marine and Cappy, Pierre and Blanco-Rodriguez, Guillermo and Levy, Nicolas and Oladosu, Oyndamola and Schmidt, Sylvie and Gasser, Romain and Rossolillo, Paola and Moog, Christiane and Ruff, Marc and Nunzio, Francesca Di and Negroni, Matteo and Lener, Daniela, Genetic Flexibility of the NKNK Motif in HIV-1 Integrases Allows Its Involvement in Multiple Functions During Infection (2018). Available at SSRN: https://ssrn.com/abstract=3208264 or http://dx.doi.org/10.2139/ssrn.3208264
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Marine Kanja

University of Strasbourg - Architecture et Réactivité de l’ARN

Strasbourg, Alsace
France

Pierre Cappy

University of Strasbourg - Architecture et Réactivité de l’ARN

Strasbourg, Alsace
France

Guillermo Blanco-Rodriguez

University of Paris-Saclay - Molecular Virology and Vaccinology Unit (VMV)

28 Rue du Docteur Roux
Paris, 75015
France

Nicolas Levy

University of Strasbourg - Chromatin Stability and DNA mobility

Strasbourg, Alsace
France

Oyndamola Oladosu

University of Strasbourg - Chromatin Stability and DNA mobility

Strasbourg, Alsace
France

Sylvie Schmidt

University of Strasbourg - Molecular Immuno-Rhumatology Laboratory

Strasbourg, Alsace
France

Romain Gasser

University of Strasbourg - Architecture et Réactivité de l’ARN

Strasbourg, Alsace
France

Paola Rossolillo

University of Strasbourg - Architecture et Réactivité de l’ARN

Strasbourg, Alsace
France

Christiane Moog

University of Strasbourg - Molecular Immuno-Rhumatology Laboratory

Strasbourg, Alsace
France

Marc Ruff

University of Strasbourg - Chromatin Stability and DNA mobility

Strasbourg, Alsace
France

Francesca Di Nunzio

University of Paris-Saclay - Molecular Virology and Vaccinology Unit (VMV)

28 Rue du Docteur Roux
Paris, 75015
France

Matteo Negroni (Contact Author)

University of Strasbourg - Architecture et Réactivité de l’ARN ( email )

Strasbourg, Alsace
France

Daniela Lener

University of Strasbourg - Architecture et Réactivité de l’ARN ( email )

Strasbourg, Alsace
France

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