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Ezrin, Radixin, and Moesin (ERM) proteins function as pleiotropic regulators of human immunodeficiency virus type 1

Yoshinao Kubo1, Hiroaki Yoshii, Haruka Kamiyama

  • 1Department of AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, National Institute of Infectious Diseases, Tokyo, Japan. yoshinao@net.nagasaki-u.ac.jp

Virology
|February 26, 2008
PubMed

Insights

Ezrin, radixin, and moesin (ERM) proteins regulate HIV-1 infection. ERM suppression impacts X4-tropic HIV-1 transduction and cell fusion, with moesin uniquely affecting R5-tropic HIV-1 entry.

Area of Science:

  • Cell Biology
  • Virology
  • Molecular Biology

Background:

  • Ezrin, radixin, and moesin (ERM) proteins link cell membrane proteins to the cytoskeleton, influencing membrane dynamics and cell structure.
  • Understanding the role of ERM proteins in the human immunodeficiency virus type 1 (HIV-1) lifecycle is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the role of ERM proteins in HIV-1 envelope (Env)-mediated transduction and cell-cell fusion.
  • To determine if ERM protein suppression affects HIV-1 infection mediated by different Env tropisms (X4- and R5-tropic).

Main Methods:

  • Utilized dominant-negative ezrin mutants and siRNA-mediated knockdown of ezrin, radixin, and moesin in human cells expressing HIV-1 receptors.
  • Assessed HIV-1 vector transduction efficiency for X4- and R5-tropic Envs.
  • Evaluated cell-cell fusion mediated by X4- and R5-tropic Envs.
  • Measured cell surface expression of HIV-1 receptors (CD4, CCR5, CXCR4).

Main Results:

  • Suppression of ERM proteins uniformly decreased transduction titers of X4-tropic HIV-1 vectors.
  • Radixin knockdown reduced R5-tropic HIV-1 vector transduction, while ezrin knockdown had no effect and moesin knockdown increased it.
  • ERM suppression did not affect cell surface receptor expression or VSV-Env-mediated transduction.
  • Knockdown of ERM proteins uniformly decreased cell-cell fusion mediated by both X4- and R5-tropic Envs.

Conclusions:

  • ERM proteins are positive regulators of X4-tropic HIV-1 infection.
  • Moesin acts as a negative regulator of R5-tropic HIV-1 infection post-membrane fusion.
  • ERM proteins differentially regulate receptor dynamics in R5- and X4-tropic HIV-1 infections, highlighting distinct mechanisms of viral entry.

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