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Phosphorylation by MAPK regulates simian immunodeficiency virus Vpx protein nuclear import and virus infectivity

Palakurthy Rajendra Kumar1, Prabhat K Singhal, Malireddi R K Subba Rao

  • 1Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics, ECIL Road, Hyderabad 500 076, India.

The Journal of Biological Chemistry
|November 24, 2004
PubMed

Insights

Host cell kinases, specifically ERK-2/MAPK, phosphorylate Simian Immunodeficiency Virus (SIV) Vpx protein, enabling nuclear transport and replication. This phosphorylation is crucial for early SIV infection stages.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Nuclear transport of viral components is essential for infection.
  • Host cell kinases play a role in regulating viral entry and replication.
  • Simian Immunodeficiency Virus (SIV) utilizes host factors for its life cycle.

Purpose of the Study:

  • To investigate the role of ERK-2/MAPK in SIV nuclear import and replication.
  • To identify the mechanism by which ERK-2/MAPK regulates Vpx function.
  • To determine the structural requirements for Vpx nuclear import.

Main Methods:

  • Virion association assays
  • MAPK pathway inhibitor treatment
  • Site-directed mutagenesis of Vpx
  • Macrophage infection assays
  • Confocal microscopy for co-localization studies

Main Results:

  • ERK-2/MAPK is associated with SIV virions and phosphorylates Vpx.
  • Inhibition of ERK-2/MAPK impairs Vpx nuclear import and viral infectivity.
  • Vpx phosphorylation is necessary for nuclear import and replication, independent of integrase and Gag matrix.
  • Specific Vpx mutations disrupt nuclear import and virion incorporation, highlighting the importance of structural integrity.

Conclusions:

  • The host cell MAPK signaling pathway regulates early SIV infection by controlling Vpx nuclear transport.
  • ERK-2/MAPK-mediated phosphorylation of Vpx is a critical step for SIV replication in non-proliferating cells.
  • Vpx incorporation into virions requires co-localization with Gag precursor and structural integrity of its helical domain.

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