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Measurement of In Vitro Integration Activity of HIV-1 Preintegration Complexes
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Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry
Doortje Borrenberghs1,2, Lieve Dirix1,2, Flore De Wit1
1Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, 3000, Belgium.
Scientific Reports
|November 11, 2016
Summary
Single-virus imaging reveals how HIV-1 pre-integration complexes (PICs) enter the nucleus. Inhibiting the IN-LEDGF/p75 interaction with LEDGINs hinders nuclear entry by stabilizing IN multimers.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Nuclear entry of HIV-1 pre-integration complexes (PICs) is essential for viral replication.
- Traditional methods provide averaged data, limiting understanding of individual PIC behavior.
Purpose of the Study:
- To investigate the dynamics of single HIV-1 PICs during nuclear entry using advanced imaging techniques.
- To elucidate the role of HIV-1 integrase (IN) and its interaction with LEDGF/p75 in nuclear import.
Main Methods:
- Single-virus fluorescence imaging to track individual HIV-1 PICs.
- Visualization of HIV-1 integrase (IN) during the infection process.
- Utilizing LEDGINs, small molecule inhibitors, to probe the IN-LEDGF/p75 interaction.
Main Results:
- Nuclear entry involves a decrease in IN molecules within PICs.
- LEDGF/p75 interaction promotes IN oligomerization in the nucleus.
- LEDGINs induce stable IN multimers, blocking nuclear entry due to size restrictions.
Conclusions:
- Single-virus imaging offers critical insights into HIV replication mechanisms.
- PIC nuclear import is regulated by IN multimerization and size, influenced by LEDGF/p75.
- Targeting the IN-LEDGF/p75 interaction with inhibitors like LEDGINs represents a potential antiviral strategy.
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