Phylogenetically Distant Viruses Use the Same BH3-Only Protein Puma to Trigger Bax/Bak-Dependent Apoptosis of

Emanuela Papaianni1, Souhayla El Maadidi2, Andrea Schejtman3

  • 1Department of Biological and Environmental Sciences, University of Messina, Via F. Stagno d'Alcontres 31, I-98166, Messina, Italy; The Institute of Translational Pharmacology, CNR, Via Fosso del Cavaliere 100, I-00133, Rome, Italy; Institute of Molecular Medicine and Cell Research, Albert Ludwigs University of Freiburg, Stefan Meier Strasse 17, D-79104, Freiburg, Germany.

Plos One
|June 2, 2015
PubMed

Insights

Viruses induce host cell apoptosis via outer mitochondrial membrane permeabilization (MOMP). This study identifies the BH3-only protein Puma as a key mediator of virus-induced MOMP and apoptosis.

Area of Science:

  • Cellular Biology
  • Virology
  • Immunology

Background:

  • Viruses can induce apoptosis in host cells through outer mitochondrial membrane permeabilization (MOMP).
  • The precise mechanisms by which viruses trigger MOMP remain unclear.
  • Anti-apoptotic proteins, including Bcl-2 homologs, can counteract virus-induced apoptosis.

Purpose of the Study:

  • To elucidate the mechanism of virus-induced MOMP and apoptosis.
  • To identify key cellular proteins involved in viral apoptosis.
  • To investigate the role of the BH3-only protein Puma in virus-induced MOMP.

Main Methods:

  • Utilized herpes simplex virus-1 (HSV-1) and Semliki Forest virus (SFV) in cell culture models.
  • Employed genetic deletion and shRNA to downregulate Puma expression.
  • Assessed apoptosis and MOMP induction in various cell types, including mouse embryonic fibroblasts, monocytes, and human colon carcinoma cells.
  • Analyzed Puma protein and mRNA levels post-infection.
  • Investigated the involvement of transcription factors p53, p73, and p65 NFκB.

Main Results:

  • Puma is identified as the major mediator of virus-induced Bax/Bak activation and MOMP.
  • Cells lacking Puma were resistant to virus-induced apoptosis, similar to Bax/Bak double-deficient cells.
  • Puma protein expression increased post-infection with both HSV-1 and SFV.
  • Puma mRNA upregulation occurred after MOMP initiation, suggesting a post-transcriptional regulatory mechanism.
  • Classical Puma transcription factors were not involved in HSV-1-induced apoptosis.

Conclusions:

  • Viruses utilize a Puma protein-dependent pathway to trigger MOMP and apoptosis in host cells.
  • Puma acts as a critical link between viral infection and the intrinsic apoptotic pathway.
  • This finding reveals a novel mechanism of viral pathogenesis and potential therapeutic targets.

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