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Peptide-based Identification of Functional Motifs and their Binding Partners
14:28

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: July 1, 2013

Dengue virus M protein contains a proapoptotic sequence referred to as ApoptoM

Adeline Catteau1, Olga Kalinina1, Marie-Christine Wagner2

  • 1Unité Postulante des Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.

The Journal of General Virology
|September 19, 2003
PubMed

Insights

The dengue virus small membrane (M) protein ectodomain triggers apoptosis in host cells. This M ectodomain initiates cell death by activating a mitochondrial pathway, with specific amino acids being crucial for this proapoptotic function.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Apoptotic cell death is a key effect of dengue (DEN) virus infections.
  • Identifying viral components responsible for inducing apoptosis is crucial for understanding DEN pathogenesis.

Purpose of the Study:

  • To investigate the role of the dengue virus small membrane (M) protein in inducing apoptosis.
  • To determine if M ectodomains from DEN viruses and related flaviviruses possess proapoptotic properties.

Main Methods:

  • Utilized enhanced green fluorescent protein (EGFP)-fused DEN proteins to study M protein function.
  • Assessed apoptosis induction in mouse neuroblastoma (Neuro 2a) and human hepatoma (HepG2) cells.
  • Investigated the role of M ectodomain localization and interaction with anti-apoptotic proteins like Bcl-2.

Main Results:

  • Intracellular production of M ectodomains from all four DEN serotypes induced apoptosis in host cells.
  • M ectodomains from Japanese encephalitis, West Nile, and yellow fever viruses also exhibited proapoptotic activity.
  • Export of the M ectodomain to the plasma membrane was essential for apoptosis initiation; Bcl-2 conferred protection, suggesting mitochondrial pathway involvement.
  • A nine-amino acid region (ApoptoM) within the M ectodomain contained intrinsic proapoptotic properties, with residue M-36 playing a modulating role.

Conclusions:

  • The dengue virus M protein ectodomain is a significant inducer of apoptosis in host cells.
  • The M ectodomain's proapoptotic activity is mediated through a mitochondrial pathway, involving specific amino acid residues.
  • Understanding the M protein's role in apoptosis is vital for developing strategies against flavivirus infections.

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