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Genome Replication and Regulation of Viral Gene Expression

Characterization of the Behavior of Functional Viral Genomes during the Early Steps of Human Immunodeficiency Virus Type 1 Infection

Vanessa Arfi, Julia Lienard, Xuan-Nhi Nguyen, Gregory Berger, Dominique Rigal, Jean-Luc Darlix, Andrea Cimarelli
Vanessa Arfi
1LaboRetro, Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France
2INSERM, U758, Lyon, France
3University of Lyon 1, IFR128 BioSciences Lyon-Gerland, Lyon-Biopole, Lyon, France
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Julia Lienard
1LaboRetro, Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France
2INSERM, U758, Lyon, France
3University of Lyon 1, IFR128 BioSciences Lyon-Gerland, Lyon-Biopole, Lyon, France
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Xuan-Nhi Nguyen
1LaboRetro, Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France
2INSERM, U758, Lyon, France
3University of Lyon 1, IFR128 BioSciences Lyon-Gerland, Lyon-Biopole, Lyon, France
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Gregory Berger
1LaboRetro, Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France
2INSERM, U758, Lyon, France
3University of Lyon 1, IFR128 BioSciences Lyon-Gerland, Lyon-Biopole, Lyon, France
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Dominique Rigal
4Etablissement Français du Sang, Lyon, France
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Jean-Luc Darlix
1LaboRetro, Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France
2INSERM, U758, Lyon, France
3University of Lyon 1, IFR128 BioSciences Lyon-Gerland, Lyon-Biopole, Lyon, France
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Andrea Cimarelli
1LaboRetro, Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France
2INSERM, U758, Lyon, France
3University of Lyon 1, IFR128 BioSciences Lyon-Gerland, Lyon-Biopole, Lyon, France
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  • For correspondence: acimarel@ens-lyon.fr
DOI: 10.1128/JVI.00429-09
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ABSTRACT

Infectious viral DNA constitutes only a small fraction of the total viral DNA produced during retroviral infection, and as such its exact behavior is largely unknown. In the present study, we characterized in detail functional viral DNA produced during the early steps of human immunodeficiency virus type 1 infection by analyzing systematically their kinetics of synthesis and integration in different target cells. In addition, we have compared the functional stability of viral nucleoprotein complexes arrested at their pre-reverse transcription state, and we have attempted to measure the kinetics of loss of capsid proteins from viral complexes through the susceptibility of the early phases of infection to cyclosporine, a known inhibitor of the interaction between viral capsid and cyclophilin A. Overall, our data suggest a model in which loss of capsid proteins from viral complexes and reverse transcription occur concomitantly and in which the susceptibility of target cells to infection results from a competition between the ability of the cellular environment to quickly destabilize viral nucleoprotein complexes and the capability of the virus to escape such targeting by engaging the reverse transcription reaction.

  • Copyright © 2009 American Society for Microbiology
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Characterization of the Behavior of Functional Viral Genomes during the Early Steps of Human Immunodeficiency Virus Type 1 Infection
Vanessa Arfi, Julia Lienard, Xuan-Nhi Nguyen, Gregory Berger, Dominique Rigal, Jean-Luc Darlix, Andrea Cimarelli
Journal of Virology Jul 2009, 83 (15) 7524-7535; DOI: 10.1128/JVI.00429-09

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Characterization of the Behavior of Functional Viral Genomes during the Early Steps of Human Immunodeficiency Virus Type 1 Infection
Vanessa Arfi, Julia Lienard, Xuan-Nhi Nguyen, Gregory Berger, Dominique Rigal, Jean-Luc Darlix, Andrea Cimarelli
Journal of Virology Jul 2009, 83 (15) 7524-7535; DOI: 10.1128/JVI.00429-09
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KEYWORDS

Genome, Viral
HIV Infections
HIV-1
virus integration

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