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Updated: Nov 27, 2025
Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
Published on: October 15, 2018
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: Triggering a Lethal Fight to Keep Control of
Sofia Kouidou1, Andigoni Malousi1, Alexandra-Zoi Andreou2
1Lab of Biological Chemistry, Medical School, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
Abstract:
The extended and diverse interference of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in multiple host functions and the diverse associated symptoms implicate its involvement in fundamental cellular regulatory processes. The activity of ten-eleven translocase 2 (TET2) responsible for selective DNA demethylation, has been recently identified as a regulator of endogenous virus inactivation and viral invasion, possibly by proteasomal deregulation of the TET2/TET3 activities. In a recent report, we presented a detailed list of factors that can be affected by TET activity, including recognition of zinc finger protein binding sites and bimodal promoters, by enhancing the flexibility of adjacent sequences. In this review, we summarize the TET-associated processes and factors that could account for SARS-CoV-2 diverse symptoms. Moreover, we provide a correlation for the observed virus-induced symptoms that have been previously associated with TET activities by in vitro and in vitro studies. These include early hypoxia, neuronal regulation, smell and taste development, liver, intestinal, and cardiomyocyte differentiation. Finally, we propose that the high mortality of SARS-CoV-2 among adult patients, the different clinical symptoms of adults compared to children, the higher risk of patients with metabolic deregulation, and the low mortality rates among women can all be accounted for by the complex balance of the three enzymes with TET activity, which is developmentally regulated. This activity is age-dependent, related to telomere homeostasis and integrity, and associated with X chromosome inactivation via (de)regulation of the responsible XIST gene expression.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts host functions by altering ten-eleven translocation (TET) enzyme activity. This review links TET deregulation to diverse COVID-19 symptoms and patient outcomes.
Area of Science:
- Epigenetics
- Virology
- Molecular Biology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits diverse effects on host functions and symptoms, suggesting involvement in fundamental cellular processes.
- Ten-eleven translocation 2 (TET2) enzymes regulate DNA demethylation and have been implicated in controlling viral invasion and endogenous virus inactivation.
- Previous work identified factors affected by TET activity, including DNA recognition sites and promoter flexibility.
Purpose of the Study:
- To review TET-associated processes and factors potentially explaining SARS-CoV-2 symptoms.
- To correlate SARS-CoV-2-induced symptoms with known TET activities from in vitro and in vivo studies.
- To propose a role for TET enzyme balance in differential COVID-19 outcomes based on age, sex, and metabolic status.
Main Methods:
- Literature review and synthesis of existing research on TET enzymes and SARS-CoV-2.
- Correlation analysis of virus-induced symptoms with established TET activities.
- Exploration of TET activity's developmental regulation, age-dependency, and link to X chromosome inactivation.
Main Results:
- TET enzyme activity is linked to various SARS-CoV-2 symptoms, including hypoxia, neurological effects, sensory loss, and organ differentiation issues.
- TET deregulation may explain differential COVID-19 severity in adults versus children, and higher risk in metabolically deregulated patients.
- Age-dependent TET activity, telomere homeostasis, and XIST gene regulation via TET enzymes are proposed factors influencing COVID-19 outcomes.
Conclusions:
- TET enzyme activity plays a crucial role in mediating the diverse cellular impacts and clinical manifestations of SARS-CoV-2 infection.
- The balance of TET enzymes, influenced by development and epigenetics, offers a framework for understanding varied COVID-19 patient responses.
- Further research into TET pathways could reveal therapeutic targets for mitigating SARS-CoV-2-associated pathology.
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