QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.104.001735v1 66/4/783    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mousnier, A. Articles by Dargemont, C. Search for Related Content PubMed PubMed Citation Articles by Mousnier, A. Articles by Dargemont, C.

Accelerated Communication

Nuclear Import of HIV-1 Integrase Is Inhibited in Vitro by Styrylquinoline Derivatives

Institut Jacques Monod, Unité Mixte de Recherche 7592, Centre National de la Recherche Scientifique, Universités Paris 6 et 7, Paris, France (A.M., C.D.); Bioalliance Pharma, Paris, France (H.L.); and Laboratoire de Biotechnologies et Pharmacologie génétique Appliquée, Unité Mixte Recherche 8113, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Cachan, Cachan, France (J.-F.M.)

Nuclear import of HIV-1 preintegration complexes (PICs) allows the virus to infect nondividing cells. Integrase (IN), the PIC-associated viral enzyme responsible for the integration of the viral genome into the host cell DNA, displays karyophilic properties and has been proposed to participate to the nuclear import of the PIC. Styrylquinolines (SQs) have been shown to block viral replication at nontoxic concentrations and to inhibit IN 3'-processing activity in vitro by competing with the DNA substrate binding. However, several lines of evidence suggested that SQs could have a postentry, preintegrative antiviral effect in infected cells. To gain new insights on the mechanism of their antiviral activity, SQs were assayed for their ability to affect nuclear import of HIV-1 IN and compared with the effect of a specific strand transfer inhibitor. Using an in vitro transport assay, we have previously shown that IN import is a saturable mechanism, thus showing that a limiting cellular factor is involved in this process. We now demonstrate that SQs specifically and efficiently inhibit in vitro nuclear import of IN without affecting other import pathways, whereas a specific strand transfer inhibitor does not affect IN import. These data suggest that SQs not only inhibit IN-DNA interaction but would also inhibit the interaction between IN and the cellular factor required for its nuclear import.

Address correspondence to: Catherine Dargemont, Institut Jacques Monod, UMR 7592 CNRS, Universités Paris 6 et 7, 2 Place Jussieu, Tour 43, 75251 Paris Cedex 05, France. E-mail: dargemont{at}ijm.jussieu.fr

This article has been cited by other articles:

				S. Rabaaoui, F. Zouhiri, A. Lancon, H. Leh, J. d'Angelo, and E. Wattel Inhibitors of Strand Transfer That Prevent Integration and Inhibit Human T-Cell Leukemia Virus Type 1 Early Replication Antimicrob. Agents Chemother., October 1, 2008; 52(10): 3532 - 3541. [Abstract] [Full Text] [PDF]