Metabolome-Driven Regulation of Adenovirus-Induced Cell Death

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.

Ceramide and Related Molecules in Viral Infections

“…Ceramide is necessary for the lytic phase of adenovirus infection through the regulation of the cellular spliceosome [ 155 ]. Of note, adenovirus induces increases in ceramide levels [ 156 ] but specifically blocks ceramide-induced apoptosis through the expression of its E1B19K anti-apoptotic protein [ 155 ].…”

Autophagy in Cancer Progression and Therapeutics

“…In addition, even wild-type adenoviruses or conditionally replicating adenoviruses (CRAds) can trigger autophagy to maintain the infected cells' viability for delivery of viral DNA and expression of adenoviral structural proteins [1]. Subsequently, infected cells die, and the viral progeny spreads to neighboring cells to continue the infection cycle [2].Autophagy is thus an essential process preventing normally functioning cells from becoming mutated or deregulated. In spite of this, abnormal autophagy is connected with various diseases, including cardio-related diseases, neurodegenerative diseases, and especially cancer [3].…”