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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.
Highlights
Our knowledge regarding the epidemiological data of coronavirus disease (COVID-19) is rapidly increasing [1,2]
The virus is thought to interfere with the cellular E3 ubiquitin ligase ring-finger system by using a two-component system: The SARS-unique domain (SUD), which can bind to a G-quadruplex through a CHY protein domain, and the papain-like protease (PL(pro))
In view of the above, it can be concluded that telomeric changes are subject to ten-eleven translocase (TET)-associated epigenetic regulation, and might be responsible for the high death rates observed among the elderly SARS-CoV-2 patients
Summary
Our knowledge regarding the epidemiological data of coronavirus disease (COVID-19) is rapidly increasing [1,2]. Efforts for targeting the COVID-19 pandemic require comprehension of the viral mechanisms and its targets, including those associated with its “unique” or “unusual” and possibly less troubling, accompanying symptoms This is important, since there is an extensive ongoing discussion with regards to the long-lasting viral consequences and the threat that. We present evidence, associating the frequent, but “unique” symptoms of SARS-CoV-2 infection with the mechanism of DNA demethylation by ten-eleven translocase (TET) activity This activity is responsible for differentiation and tissue-specific regulation of gene expression, regulation of X chromosome inactivation, age-dependent and telomere-related activity, and regulated in vivo by a process similar to that disrupted by SARS-CoV in the process of ACE2 deactivation
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