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Journal of Virology, August 2009, p. 7524-7535, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00429-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Vanessa Arfi,1,2,3 Julia Lienard,1,2,3 Xuan-Nhi Nguyen,1,2,3 Gregory Berger,1,2,3 Dominique Rigal,4 Jean-Luc Darlix,1,2,3 and Andrea Cimarelli1,2,3*

LaboRetro, Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France,1 INSERM, U758, Lyon, France,2 University of Lyon 1, IFR128 BioSciences Lyon-Gerland, Lyon-Biopole, Lyon, France,3 Etablissement Français du Sang, Lyon, France4

Received 27 February 2009/ Accepted 13 May 2009

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.


* Corresponding author. Mailing address: LaboRetro, Department of Human Virology, ENS-Lyon INSERM, U758, 46 Allée d'Italie, 69364 Lyon, France. Phone: (33) 4 72728696. Fax: (33) 4 72728137. E-mail: acimarel{at}ens-lyon.fr

{triangledown} Published ahead of print on 20 May 2009.


Journal of Virology, August 2009, p. 7524-7535, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00429-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.