Pathogens Hijack Host Cell Metabolism: Intracellular Infection as a Driver of Warburg Effect in Cancer & Other [...], 2021, Proal & VanElzakker

[Kitty]

Pathogens Hijack Host Cell Metabolism: Intracellular Infection as a Driver of the Warburg Effect in Cancer and Other Chronic Inflammatory Conditions

Amy D. Proal and Michael B. VanElzakker, 2021

This hypothesis piece discusses metabolic shift in a broad range of chronic conditions, but as it may well be relevant to ME, I thought it might be okay to post it here.


https://ij.hapres.com/htmls/IJ_1341_Detail.html

"The Warburg effect refers to a metabolic state in which cells preferentially use aerobic glycolysis rather than oxidative phosphorylation to generate ATP and macromolecules. A number of chronic inflammatory conditions are characterized by host cells that adopt a sustained, pathological Warburg-like metabolism. In cancer, previously healthy cells shift into a Warburg state centered on rapid energy production and increased cell proliferation that drives tumor formation...

The question of why host cells in patients with cancer and other chronic inflammatory conditions adapt a pathological Warburg-like metabolism is a matter of debate. This review/hypothesis piece explores how intracellular infection can contribute to this Warburg metabolism or related pathological metabolic states. We detail molecular mechanisms by which viral, bacterial, and protozoan intracellular pathogens can induce, or contribute to, a Warburg-like metabolism in infected host cells in order to meet their own replication and nutritional needs..."

 

[mat]

Very interesting hypothesis indeed, especially for the hypothesis of ME as a latent pathogen disease.

Extending this idea in the context of SARS-CoV-2, this paper hasn't been referenced in this survey.

The key role of Warburg effect in SARS-CoV-2 replication and associated inflammatory response

Current mortality due to the Covid-19 pandemic (approximately 1.2 million by November 2020) demonstrates the lack of an effective treatment. As replication of many viruses - including MERS-CoV - is supported by enhanced aerobic glycolysis, we hypothesized that SARS-CoV-2 replication in host cells (especially airway cells) is reliant upon altered glucose metabolism. This metabolism is similar to the Warburg effect well studied in cancer. Counteracting two main pathways (PI3K/AKT and MAPK/ERK signaling) sustaining aerobic glycolysis inhibits MERS-CoV replication and thus, very likely that of SARS-CoV-2, which shares many similarities with MERS-CoV. The Warburg effect appears to be involved in several steps of COVID-19 infection. Once induced by hypoxia, the Warburg effect becomes active in lung endothelial cells, particularly in the presence of atherosclerosis, thereby promoting vasoconstriction and micro thrombosis. Aerobic glycolysis also supports activation of pro-inflammatory cells such as neutrophils and M1 macrophages. As the anti-inflammatory response and reparative process is performed by M2 macrophages reliant on oxidative metabolism, we speculated that the switch to oxidative metabolism in M2 macrophages would not occur at the appropriate time due to an uncontrolled pro-inflammatory cascade. Aging, mitochondrial senescence and enzyme dysfunction, AMPK downregulation and p53 inactivation could all play a role in this key biochemical event. Understanding the role of the Warburg effect in COVID-19 can be essential to developing molecules reducing infectivity, arresting endothelial cells activation and the pro-inflammatory cascade.

doi: 10.1016/j.biochi.2020.11.010