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

Aurélie Mousnier, Hervé Leh, Jean-François Mouscadet and Catherine Dargemont
Molecular Pharmacology October 2004, 66 (4) 783-788; DOI: https://doi.org/10.1124/mol.104.001735
Aurélie Mousnier
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Hervé Leh
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Jean-François Mouscadet
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Catherine Dargemont
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Abstract

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.

  • Received April 22, 2004.
  • Accepted July 8, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 66 (4)
Molecular Pharmacology
Vol. 66, Issue 4
1 Oct 2004
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Nuclear Import of HIV-1 Integrase Is Inhibited in Vitro by Styrylquinoline Derivatives

Aurélie Mousnier, Hervé Leh, Jean-François Mouscadet and Catherine Dargemont
Molecular Pharmacology October 1, 2004, 66 (4) 783-788; DOI: https://doi.org/10.1124/mol.104.001735

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

Aurélie Mousnier, Hervé Leh, Jean-François Mouscadet and Catherine Dargemont
Molecular Pharmacology October 1, 2004, 66 (4) 783-788; DOI: https://doi.org/10.1124/mol.104.001735
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