JVI Accepts, published online ahead of print on 4 November 2009

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J. Virol. doi:10.1128/JVI.01952-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Analysis of the viral elements required in the nuclear import of HIV-1 DNA

Lise Rivière, Jean-Luc Darlix, and Andrea Cimarelli^*

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

^* To whom correspondence should be addressed. Email: acimarel{at}ens-lyon.fr.

HIV-1 possesses an exquisite ability to infect cells independently from their cycling status by undergoing an active phase of nuclear import through the nuclear pore. This property has been ascribed to the presence of karyophilic elements present in viral nucleoprotein complexes such as the Matrix protein (MA), Vpr, the Integrase (IN) and a cis-acting structure present in the newly synthesized DNA, the DNA flap. However, their role in nuclear import remains controversial at best. In the present study, we carried out a comprehensive analysis of the role of these elements in nuclear import in a comparison between several primary cell types, including stimulated lymphocytes, macrophages and dendritic cells. We show that despite the fact that none of these elements is absolutely required for nuclear import, disruption of the central polypurine tract- central termination sequence clearly affects the kinetics of viral DNA entry into the nucleus. This effect is independent of the cell cycle status of the target cells and is observed in cycling as well as in non-dividing primary cells, suggesting that nuclear import of viral DNA may occur similarly under both conditions. Nonetheless, this study indicates that other components are utilized along with the cPPT-CTS for an efficient entry of viral DNA into the nucleus.