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Nucleic Acids Research, 2003, Vol. 31, No. 18 5425-5432
© 2003 Oxford University Press

DNA condensation by the nucleocapsid protein of HIV-1: a mechanism ensuring DNA protection

G. Krishnamoorthy*,1,4, Bernard Roques2, Jean-Luc Darlix3 and Yves Mély1

1 Laboratoire de Pharmacologie et Physicochimie des interactions cellulaires et moléculaires, UMR 7034 du CNRS, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, 74 Route du Rhin, 67401 Illkirch, France, 2 Département de Pharmacochimie Moléculaire et Structurale, INSERM U266, Faculté de Pharmacie, 4, Avenue de l’Observatoire, 75270 Paris Cedex 06, France, 3 LaboRétro, Unité de Virologie Humaine INSERM, Ecole Normale Supérieure de Lyon, 46 allée d’Italie, 69364 Lyon, France and 4 on leave from Tata Institute of Fundamental Research, Department of Chemical Sciences, Homi Bhabha Road, Mumbai 400 005, India

*To whom correspondence should be addressed. Tel: +91 22 2280 4545; Fax: +91 22 2280 4610; Email: gk{at}tifr.res.in
Correspondence may also be addressed to Yves Mély. Tel: +33 03 90 24 42 63; Fax: +33 03 90 24 43 12; Email: mely{at}aspirine.u-strasbg.fr

The nucleocapsid (NC) protein NCp7 of the immunodeficiency virus type 1 is a small basic protein with two zinc finger motifs. NCp7 has key roles in virus replication and structure, which rely on its interactions with nucleic acids. Although most interactions involve RNAs, binding to the viral DNA is thought to be of importance to achieve protection of the DNA against cellular nucleases and its integration into the host genome. We investigated the interaction of NCp7 with plasmid DNA as a model system. The fluorescence probe YOYO-1 was used as the reporter. Binding of NCp7 to DNA caused DNA condensation, as inferred from the dramatic decrease in YOYO-1 fluorescence. Efficient condensation of DNA required the full length NCp7 with the zinc fingers. The fingerless peptide was less efficient in condensing DNA. Binding of both these NC peptides led to freezing of the segmental dynamics of DNA as revealed by anisotropy decay kinetics of YOYO-1. The truncated peptide NC(12–55) which retains the zinc fingers did not lead to DNA condensation despite its ability to bind and partially freeze the segmental motion of DNA. We propose that the histone-like property of NCp7 leading to DNA condensation contributes to viral DNA stability, in vivo.


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