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

1999 ◽  
Vol 73 (12) ◽  
pp. 10000-10009 ◽  
Author(s):  
Lionel Berthoux ◽  
Christine Péchoux ◽  
Jean-Luc Darlix
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Synthesis ◽  
Nucleocapsid Protein ◽  
Proviral Dna ◽  
Immunodeficiency Virus ◽  
Major Structural Component ◽  
Key Factor ◽  
New Compounds ◽  
Virion Core

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.

scholarly journals Role of the N-Terminal Zinc Finger of Human Immunodeficiency Virus Type 1 Nucleocapsid Protein in Virus Structure and Replication

1998 ◽  
Vol 72 (5) ◽  
pp. 4442-4447 ◽  
Author(s):  
Valérie Tanchou ◽  
Didier Decimo ◽  
Christine Péchoux ◽  
Daniela Lener ◽  
Véronique Rogemond ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Synthesis ◽  
Zinc Finger ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Nucleocapsid Protein ◽  
Proviral Dna ◽  
Immunodeficiency Virus ◽  
Function Relationship

ABSTRACT Nucleocapsid protein (NCp7) of human immunodeficiency virus type 1 is found covering the genomic RNA in the interior of the viral particle. It is a highly basic protein with two zinc fingers of the form CX2CX4HX4C which exhibit strong affinity for a zinc cation. To study the structure-function relationship of the N-terminal zinc finger of NCp7, this domain was either deleted or changed to CX2CX4CX4C. We examined virus formation and structure as well as proviral DNA synthesis. Our data show that these two NC mutations result in the formation of particles with an abnormal core morphology and impair the end of proviral DNA synthesis, leading to noninfectious viruses.

scholarly journals Mutations in the Primer Grip of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Impair Proviral DNA Synthesis and Virion Maturation

1998 ◽  
Vol 72 (9) ◽  
pp. 7676-7680 ◽  
Author(s):  
Qiang Yu ◽  
Michele Ottmann ◽  
Christine Pechoux ◽  
Stuart Le Grice ◽  
Jean-Luc Darlix
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Dna Synthesis ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Virus Assembly ◽  
Conserved Residues ◽  
Proviral Dna ◽  
Immunodeficiency Virus

ABSTRACT This report describes the effects of mutating highly conserved residues in the primer grip domain of human immunodeficiency virus type 1 reverse transcriptase (RT) on virus formation and infectivity. Among a series of RT mutant viruses, three (M230A, L234D, and W239A) were found to be noninfectious or very poorly infectious. Our data indicate that these mutations in RT caused severe defects in proviral DNA synthesis. Interestingly, assembly and maturation of mutant virus M230A were similar to those of the wild type, while mutants L234D and W239A showed impaired maturation. The immature morphology of RT mutants L234D and W239A is due at least in part to premature cleavage of the gag-pol precursor, prior to virion budding, indicating that intracellular stability of Pr160 gag-pol is of key importance during virus assembly.

scholarly journals Human Immunodeficiency Virus Type 1 Nucleocapsid Protein Nuclear Localization Mediates Early Viral mRNA Expression

2002 ◽  
Vol 76 (20) ◽  
pp. 10444-10454 ◽  
Author(s):  
Jielin Zhang ◽  
Clyde S. Crumpacker
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mrna Expression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Nucleocapsid Protein ◽  
Viral Mrna ◽  
Genomic Rna ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT An important aspect of the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection is the ability of the virus to replicate in the host vigorously without a latent phase and to kill cells with a dynamic turnover of 1.8 × 109 cells/day and 10.3 × 109 virions/24 h. The transcription of HIV-1 RNA in acute infection occurs at two stages; the transcription of viral spliced mRNA occurs early, and the transcription of viral genomic RNA occurs later. The HIV-1 Tat protein is translated from the early spliced mRNA and is critical for HIV-1 genomic RNA expression. The cellular transcription factors are important for HIV-1 early spliced mRNA expression. In this study we show that virion nucleocapsid protein (NC) has a role in expression of HIV-1 early spliced mRNA. The HIV-1 NC migrates from the cytoplasm to the nucleus and accumulates in the nucleus at 18 h postinfection. Mutations on HIV-1 NC zinc fingers change the pattern of early viral spliced mRNA expression and result in a delayed expression of early viral mRNA in HIV-infected cells. This delayed HIV-1 early spliced mRNA expression occurs after proviral DNA has been integrated into the cellular genome, as shown by a quantitative integration assay. These results show that virion NC plays an important role in inducing HIV-1 early mRNA expression and contributes to the rapid viral replication that occurs during HIV-1 infection.

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