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Cell killing by HIV-1 protease.

Raquel Blanco1, Luis Carrasco, Iván Ventoso

  • 1Centro de Biologia Molecular Severo Ochoa Consejo Superior Investigaciones Cientificas-Universidad Autónoma de Madrid, Spain.

The Journal of Biological Chemistry
|October 9, 2002
PubMed
Summary

Human immunodeficiency virus protease (HIV-1 PR) causes cell death and lysis in both yeast and mammalian cells. This viral protease activity leads to membrane damage and cell breakdown, contributing to HIV-1 cytopathogenesis.

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Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • The human immunodeficiency virus protease (HIV-1 PR) is essential for viral maturation.
  • Understanding the cytopathic effects of HIV-1 PR is crucial for comprehending HIV-1 pathogenesis.
  • Previous studies have not fully elucidated the direct cellular effects of HIV-1 PR expression.

Purpose of the Study:

  • To investigate the cytopathic effects of expressing human immunodeficiency virus protease (HIV-1 PR) in Saccharomyces cerevisiae and mammalian cells.
  • To determine if the observed lytic phenotype is specific to HIV-1 PR.
  • To explore the mechanisms underlying HIV-1 PR-induced cell death.

Main Methods:

  • Inducible expression of HIV-1 PR in yeast (Saccharomyces cerevisiae) and mammalian cells (COS7).
  • Observation of cell growth, viability, plasma membrane integrity, and cell wall structure.
  • Comparison of HIV-1 PR effects with other toxic viral proteins (poliovirus 2A protease, 2BC protein).
  • Analysis of cell death pathways (apoptosis vs. necrosis).

Main Results:

  • HIV-1 PR expression arrested yeast growth, leading to cell lysis characterized by plasma membrane and cell wall damage.
  • The lytic phenotype induced by HIV-1 PR in yeast was distinct from that caused by poliovirus proteases.
  • Mammalian cells expressing HIV-1 PR also exhibited increased membrane permeability and lysis via necrosis, without apoptosis.
  • Morphological changes in both yeast and mammalian cells induced by HIV-1 PR were remarkably similar.

Conclusions:

  • HIV-1 PR possesses a unique cytolytic activity that affects both yeast and mammalian cells.
  • The protease directly induces cell membrane damage and lysis, contributing to HIV-1 cytopathogenesis.
  • This study provides novel insights into the direct cellular toxicity of HIV-1 PR and its role in disease progression.

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