Multiple effects of an anti-human immunodeficiency virus nucleocapsid inhibitor on virus morphology and replication.
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.
Berthoux
L
L
LaboRetro, Unité de Virologie Humaine INSERM-ENS no. 412, Ecole Normale Supérieure, 69364 Lyon Cedex 07, France.
Péchoux
C
C
Darlix
J L
JL
D019380:Anti-HIV Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002213:Capsid / Q000037:antagonists & inhibitors*; D036022:Capsid Proteins; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis / Q000187:drug effects; D015683:Gene Products, gag / Q000037:antagonists & inhibitors*; D054303:HIV Reverse Transcriptase / Q000096:biosynthesis / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D011533:Proviruses / Q000235:genetics; D012194:RNA-Directed DNA Polymerase; D014407:Tumor Cells, Cultured; D014764:Viral Proteins; D014771:Virion / Q000187:drug effects / Q000648:ultrastructure; D014779:Virus Replication / Q000187:drug effects*; D054301:gag Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D001549:Benzamides; D036022:Capsid Proteins; C100805:DIBA-1; D004279:DNA, Viral; D015683:Gene Products, gag; C071884:NCP7 protein, Human immunodeficiency virus 1; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase