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HIV-1 infection requires a functional integrase NLS
M Bouyac-Bertoia1, J D Dvorin, R A Fouchier
1Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Molecular Cell
|June 8, 2001
Summary
A novel nuclear localization signal (NLS) in HIV-1 integrase (IN) is essential for virus replication. This IN NLS facilitates nuclear entry of viral DNA and IN protein, crucial for infecting all cells.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Human Immunodeficiency Virus type 1 (HIV-1) can productively infect nondividing cells.
- This capability is partly due to active nuclear import of postentry viral nucleoprotein complexes.
Purpose of the Study:
- To identify novel factors contributing to HIV-1 nuclear import and replication.
- To investigate the role of viral integrase (IN) in the infection of both dividing and nondividing cells.
Main Methods:
- Identification and characterization of a novel nuclear localization signal (NLS) within the HIV-1 integrase (IN) protein.
- Assessing the impact of the IN NLS on viral DNA and IN protein nuclear accumulation during infection.
- Evaluating the necessity of the IN NLS for viral replication in both dividing and nondividing cell types.
Main Results:
- A novel NLS was identified in the HIV-1 integrase (IN) protein.
- This IN NLS is crucial for the efficient nuclear accumulation of viral DNA and IN protein during early infection stages.
- The IN NLS is essential for HIV-1 replication in both dividing and nondividing cells, independent of its catalytic activity.
Conclusions:
- The identified IN NLS is a key determinant for HIV-1 replication across different cell types.
- Nuclear import of viral nucleoprotein complexes via host cell machinery is critical for HIV-1 infection.
- Targeting this IN NLS could represent a strategy to inhibit HIV-1 infection universally.