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Journal of Virology, December 1999, p. 10000-10009, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Multiple Effects of an Anti-Human Immunodeficiency Virus Nucleocapsid Inhibitor on Virus Morphology and Replication

Lionel Berthoux,dagger Christine Péchoux, and Jean-Luc Darlix*

LaboRetro, Unité de Virologie Humaine INSERM-ENS no. 412, Ecole Normale Supérieure, 69364 Lyon Cedex 07, France

Received 16 June 1999/Accepted 30 August 1999

Human immunodeficiency virus type 1 nucleocapsid protein is a major structural component of the virion core and a key factor involved in proviral DNA synthesis and virus formation. 2,2'-Dithiobenzamides (DIBA-1) and related compounds that are inhibitors of NCp7 are thought to eject zinc ions from NCp7 zinc fingers, inhibiting the maturation of virion proteins. Here, we show that the presence of DIBA-1 at the time of virus formation causes morphological malformations of the virus and reduces proviral DNA synthesis. Thus, it seems that DIBA-1 is responsible for a "core-freezing effect," as shown by electron microscopy analyses. DIBA-1 can also directly interfere with the fate of the newly made proviral DNA in a manner independent of its effects on virion core formation. These data strongly suggest that nucleocapsid protein is a prime target for new compounds aimed at inhibiting human immunodeficiency virus and other retroviruses.

* Corresponding author. Mailing address: LaboRetro, Unité de Virologie Humaine INSERM-ENS #412, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon, Cedex 07, France. Phone: 33-4-72-72-81-69. Fax: 33-4-72-72-87-77. E-mail: Jean-Luc.Darlix{at}ens-lyon.fr.

dagger Present address: Myles H. Thaler Center, University of Virginia, Charlottesville, VA 22908.

Journal of Virology, December 1999, p. 10000-10009, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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