Deciphering the miR-29c-3p / TET3 regulatory axis within the SARS-CoV-2-infected midbrain

Abigail Dickerson; Andreea Cruceanu; Bishwa R Pokharel; Niska Majumdar; Frank Williams; Keerthana Surabhi; Erzsebet Maria Szatmari; Jeffrey B Eells; Paul P Cook; Shaw M Akula

doi:10.1016/j.virol.2026.110989

Deciphering the miR-29c-3p / TET3 regulatory axis within the SARS-CoV-2-infected midbrain

Virology. 2026 Jun 3:623:110989. doi: 10.1016/j.virol.2026.110989. Online ahead of print.

Affiliations

¹ Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA.
² Department of Physical Therapy, College of Allied Health Sciences, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA.
³ Department of Physical Therapy, College of Allied Health Sciences, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA; Max Planck Florida Institute for Neuroscience, 1 Max Planck Way, Jupiter, FL, 33458, USA.
⁴ Department of Molecular Biomedical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC, 27606, USA.
⁵ Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA. Electronic address: cookp@ecu.edu.
⁶ Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA; Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA. Electronic address: akulas@ecu.edu.

PMID: 42259181
DOI: 10.1016/j.virol.2026.110989

Abstract

Long COVID is increasingly associated with persistent neurological symptoms. Bioinformatic analysis identified multiple predicted miR-29c-3p binding sites in the 3'-UTR of Ten-Eleven-Translocation 3 (TET3). Luciferase reporter assays demonstrated that the miR-29c-3p is likely to bind an 8 base pair (bp) sequence within the 3'-UTR of TET3, supporting TET3 as a direct regulatory target. In vivo, an inverse relationship between miR-29c-3p and TET3 expression was observed in virus-positive midbrains from K18-hACE2 mice, while virus-negative and mock-infected midbrains showed no significant changes. The observation that only virus-positive brains showed decreased miR-29c-3p supports an alternative hypothesis that low base levels of miR-29c-3p expression may predispose the brain to viral neuro-invasion. Overall, miR-29c-3p > TET3 signaling emerges as a potential regulator of SARS-CoV-2-induced neurological consequences that warrants further investigation.

Keywords: Long COVID; SARS-CoV-2; TET3; miR-29c-3p; miRNA.