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.

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.

Related Concept Videos

Regulation of Metabolism01:19

Regulation of Metabolism

Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
10.8K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
8.4K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.8K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
7.2K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
5.9K