Related Experiment Video
Updated: Apr 11, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
Published on: October 5, 2012
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.
Abstract:
Viruses can trigger apoptosis of infected host cells if not counteracted by cellular or viral anti-apoptotic proteins. These protective proteins either inhibit the activation of caspases or they act as Bcl-2 homologs to prevent Bax/Bak-mediated outer mitochondrial membrane permeabilization (MOMP). The exact mechanism by which viruses trigger MOMP has however remained enigmatic. Here we use two distinct types of viruses, a double stranded DNA virus, herpes simplex virus-1 (HSV-1) and a positive sense, single stranded RNA virus, Semliki Forest virus (SFV) to show that the BH3-only protein Puma is the major mediator of virus-induced Bax/Bak activation and MOMP induction. Indeed, when Puma was genetically deleted or downregulated by shRNA, mouse embryonic fibroblasts and IL-3-dependent monocytes as well as human colon carcinoma cells were as resistant to virus-induced apoptosis as their Bax/Bak double deficient counterparts (Bax/Bak-/-). Puma protein expression started to augment after 2 h postinfection with both viruses. Puma mRNA levels increased as well, but this occurred after apoptosis initiation (MOMP) because it was blocked in cells lacking Bax/Bak or overexpressing Bcl-xL. Moreover, none of the classical Puma transcription factors such as p53, p73 or p65 NFκB were involved in HSV-1-induced apoptosis. Our data suggest that viruses use a Puma protein-dependent mechanism to trigger MOMP and apoptosis in host cells.
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.
More Related Videos
Related Concept Videos
The Intrinsic Apoptotic Pathway
Caspases
The Extrinsic Apoptotic Pathway
Viruses of Archaea
Regulation of Bacterial Virulence
DNA Bacteriophages

