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In vitro Uncoating of HIV-1 Cores
Published on: November 8, 2011
Human immunodeficiency virus type 1 virion density is not determined by nucleocapsid basic residues
1Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Journal of Virology
|July 11, 2000
Summary
Disrupting basic residues in HIV-1 nucleocapsid (NC) significantly impairs Gag-Gag interaction essential for virus assembly. However, this disruption minimally affects virion density, suggesting distinct genetic controls for these processes.
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- Human immunodeficiency virus type 1 (HIV-1) Gag polyprotein drives virion assembly and release.
- Gag polymerization forms the viral shell, crucial for nascent virion structure.
- The nucleocapsid (NC) domain's basic residues are implicated in Gag polymerization (I domain).
Purpose of the Study:
- To investigate the role of HIV-1 NC basic residues in Gag-Gag interaction and virion density.
- To determine if NC basic residues are the primary determinants of the I domain and virion density.
- To analyze mutants with disrupted NC basic residues, including an alanine replacement mutant.
Main Methods:
- Isopycnic centrifugation to assess virion density.
- Functional mapping of the Gag polymerization (I) domain.
- Site-directed mutagenesis of HIV-1 NC basic residues.
Main Results:
- Disruption of HIV-1 NC basic residues profoundly impacts Gag-Gag interaction.
- Minimal effect observed on the density of produced virions despite altered Gag-Gag interaction.
- A mutant with all NC basic residues replaced by alanine showed significant effects on Gag-Gag interaction but not density.
Conclusions:
- The determinants of the HIV-1 I domain and virion density are genetically separable.
- NC basic residues are critical for Gag-Gag interaction but not the sole determinants of virion density.
- Findings challenge the assumption that virion density directly reflects Gag-Gag interaction efficiency.
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