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A novel nuclear export activity in HIV-1 matrix protein required for viral replication

S Dupont1, N Sharova, C DéHoratius

  • 1Howard Hughes Medical Institute and Program in Molecular Medicine at the University of Massachusetts Medical Center, Worcester 01605, USA.

Nature
|December 22, 1999
PubMed

Insights

Human immunodeficiency virus type-1 (HIV-1) matrix (MA) protein has a novel nuclear export function. This function is crucial for HIV-1 replication, ensuring viral components are correctly localized for assembly.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Human immunodeficiency virus type-1 (HIV-1) replicates in non-dividing cells.
  • The HIV-1 matrix (MA) protein, part of Pr55 gag, has a nuclear localization signal (NLS) for nuclear import.
  • MA also directs viral RNA to the plasma membrane for assembly, but the mechanism is unclear.

Purpose of the Study:

  • To investigate the opposing targeting functions of the HIV-1 MA protein.
  • To identify the mechanism by which MA mediates both nuclear import and cytoplasmic localization of viral components.

Main Methods:

  • Investigated MA's role in nuclear export using mammalian cells and yeast.
  • Utilized a mutant MA (MA-M4) to disrupt the identified nuclear export signal.
  • Assessed the localization of Pr55 gag and viral RNA in cells with wild-type and mutant MA.

Main Results:

  • Demonstrated a previously undescribed nuclear export activity of MA, independent of canonical signals.
  • Nuclear export is mediated by the Crm1p pathway.
  • A mutation disrupting MA's nuclear export signal (MA-M4) caused mislocalization of Pr55 and viral RNA to the nucleus, severely impairing viral replication.
  • MA-M4 exhibited dominant-negative effects on wild-type MA's function.

Conclusions:

  • The MA protein possesses a critical nuclear export signal (NES).
  • This MA NES counteracts the MA NLS, ensuring cytoplasmic localization of viral components for efficient virion assembly.
  • The MA NES is essential for effective HIV-1 replication.

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