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Mitogen-activated protein kinase phosphorylates and regulates the HIV-1 Vif protein

X Yang1, D Gabuzda

  • 1Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.

The Journal of Biological Chemistry
|October 29, 1998
PubMed

Insights

The human immunodeficiency virus type 1 (HIV-1) Vif protein is phosphorylated by p44/42 mitogen-activated protein kinase (MAPK). This phosphorylation regulates HIV-1 replication and infectivity, revealing a novel regulatory mechanism.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Signaling

Background:

  • The human immunodeficiency virus type 1 (HIV-1) Vif protein is essential for viral replication and infectivity.
  • Understanding the regulation of Vif protein function is crucial for developing antiviral strategies.

Purpose of the Study:

  • To investigate the role of p44/42 mitogen-activated protein kinase (MAPK) in the regulation of HIV-1 Vif protein.
  • To identify the specific phosphorylation sites on Vif by MAPK and their functional significance.

Main Methods:

  • In vitro and in vivo phosphorylation assays.
  • Two-dimensional tryptic phosphopeptide mapping and radioactive peptide sequencing.
  • Site-directed mutagenesis of Vif phosphorylation sites.

Main Results:

  • HIV-1 Vif protein is phosphorylated by MAPK on serine and threonine residues, specifically at Thr96 and Ser165.
  • These phosphorylation sites do not conform to canonical MAPK consensus sequences, suggesting novel recognition mechanisms.
  • Mutation of the conserved Thr96 site significantly impairs Vif activity and inhibits HIV-1 replication.

Conclusions:

  • MAPK directly regulates HIV-1 replication and infectivity through phosphorylation of the Vif protein.
  • This study identifies a novel mechanism for HIV-1 activation by extracellular stimuli, mediated by MAPK-dependent Vif phosphorylation.

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