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PMID: 10559314 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Multiple effects of an anti-human immunodeficiency virus nucleocapsid inhibitor on virus morphology and replication.

Journal of virology ·Vol. 73 ·No. 12 ·1999-12-00 ·Pages 10000-9

Berthoux L, Péchoux C, Darlix JL

Abstract

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.

MeSH Terms
Anti-HIV Agents/pharmacology Benzamides/pharmacology Capsid/antagonists & inhibitors Capsid Proteins DNA Replication/drug effects DNA, Viral/biosynthesis,drug effects Gene Products, gag/antagonists & inhibitors HIV Reverse Transcriptase/biosynthesis,drug effects HIV-1/drug effects,physiology,ultrastructure HeLa Cells Humans Proviruses/genetics RNA-Directed DNA Polymerase Tumor Cells, Cultured Viral Proteins Virion/drug effects,ultrastructure Virus Replication/drug effects gag Gene Products, Human Immunodeficiency Virus
Chemicals
Anti-HIV Agents Benzamides Capsid Proteins DIBA-1 DNA, Viral Gene Products, gag NCP7 protein, Human immunodeficiency virus 1 Viral Proteins gag Gene Products, Human Immunodeficiency Virus HIV Reverse Transcriptase RNA-Directed DNA Polymerase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Berthoux L
LaboRetro, Unité de Virologie Humaine INSERM-ENS no. 412, Ecole Normale Supérieure, 69364 Lyon Cedex 07, France.
Péchoux C
Darlix J L
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.73.12.10000-10009.1999
Published
1999-12-00
Pages
10000-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC113051
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.73.12.10000-10009.1999 PMC Full Text View journal details
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