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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
PubMed
Summary
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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.

Related Experiment Videos

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.