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Metabolome-Driven Regulation of Adenovirus-Induced Cell Death

Journal

Publisher

MDPI
DOI: 10.3390/ijms22010464

Keywords

autophagy; viruses; metabolites

Funding

  1. Ministry of Science and Higher Education of the Russian Federation [075-15-2020-926]

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Adenovirus infection can result in sharp fluctuations in intracellular metabolite levels, leading to various types of cell death associated with changes in metabolic profiles. Experimental data suggest that changes in the metabolome precede cell death in most cases.
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.

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