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Published on: October 21, 2012
Metabolome-Driven Regulation of Adenovirus-Induced Cell Death
Anastasia Laevskaya1, Anton Borovjagin2, Peter S Timashev3,4,5
1Group of Experimental Biotherapy and Diagnostic, Institute for Regenerative Medicine, World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
Abstract:
A viral infection that involves virus invasion, protein synthesis, and virion assembly is typically accompanied by sharp fluctuations in the intracellular levels of metabolites. Under certain conditions, dramatic metabolic shifts can result in various types of cell death. Here, we review different types of adenovirus-induced cell death associated with changes in metabolic profiles of the infected cells. As evidenced by experimental data, in most cases changes in the metabolome precede cell death rather than represent its consequence. In our previous study, the induction of autophagic cell death was observed following adenovirus-mediated lactate production, acetyl-CoA accumulation, and ATP release, while apoptosis was demonstrated to be modulated by alterations in acetate and asparagine metabolism. On the other hand, adenovirus-induced ROS production and ATP depletion were demonstrated to play a significant role in the process of necrotic cell death. Interestingly, the accumulation of ceramide compounds was found to contribute to the induction of all the three types of cell death mentioned above. Eventually, the characterization of metabolite analysis could help in uncovering the molecular mechanism of adenovirus-mediated cell death induction and contribute to the development of efficacious oncolytic adenoviral vectors.
Insights
Adenovirus infection alters cell metabolism, leading to distinct cell death types like apoptosis and necrosis. Metabolomic analysis reveals these metabolic shifts precede cell death, aiding in oncolytic vector development.
Area of Science:
- Virology
- Cell Biology
- Metabolomics
Background:
- Viral infections, including adenovirus, cause significant intracellular metabolic fluctuations.
- These metabolic shifts can trigger various forms of programmed cell death.
- Understanding these metabolic changes is crucial for deciphering viral pathogenesis.
Purpose of the Study:
- To review adenovirus-induced cell death mechanisms.
- To correlate metabolic profile changes with specific cell death pathways.
- To highlight the role of metabolomics in understanding adenovirus-mediated cell death.
Main Methods:
- Review of experimental data on adenovirus-infected cells.
- Analysis of metabolic profiles and their correlation with cell death.
- Examination of specific metabolites involved in different cell death types.
Main Results:
- Metabolome changes generally precede adenovirus-induced cell death.
- Autophagic cell death linked to lactate, acetyl-CoA, and ATP release.
- Apoptosis modulated by acetate and asparagine metabolism.
- Necrotic cell death associated with ROS production and ATP depletion.
- Ceramide accumulation contributes to all three cell death types.
Conclusions:
- Metabolite analysis is key to understanding adenovirus-mediated cell death.
- Characterizing metabolic shifts can inform the development of oncolytic adenoviral vectors.
- Adenovirus-induced metabolic reprogramming offers therapeutic targets.
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