current
February 22nd, 2021 at 5:27pm
UPDATED PRE-PRINT NOW AVAILABLE
The manuscript corresponding to this pre-print on BioRxiv has been accepted for publication in the journal Cell. The publisher has produced a journal pre-proof that is available here and is registered under this DOI - 10.1016/j.cell.2022.01.024.
New datasets from the revised manuscript are available in the ExperimentSets tab in addition to those described in the original BioRxiv pre-print.
This record will be updated with the PubMed ID and information once the article is officially published.
Overview
Abstract
Olfaction relies on a coordinated partnership between odorant flow and neuronal communication. Disruption in our ability to detect odors, or anosmia, has emerged as a hallmark symptom of infection with SARS-CoV-2, yet the mechanism behind this abrupt sensory deficit remains elusive. Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (ORs) as well as key components of their signaling pathway. OR downregulation likely represents a non-cell autonomous effect, since SARS-CoV-2 detection in OSNs is extremely rare both in human and hamster OEs. A likely explanation for the reduction of OR transcription is the striking reorganization of nuclear architecture observed in the OSN lineage, which disrupts multi-chromosomal compartments regulating OR expression in humans and hamsters. Our experiments uncover a novel molecular mechanism by which a virus with a very selective tropism can elicit persistent transcriptional changes in cells that evade it, contributing to the severity of COVID-19.
Authors
Zazhytska M • Kodra A • Hoagland DA • Fullard JF • Shayya H • Omer A • Firestein S • Gong Q • Canoll PD • Goldman JE • Roussos P • tenOever BR • Overdevest JB • Lomvardas S
Link
Journal
bioRxiv : the preprint server for biology
doi:10.1101/2021.02.09.430314
Published
February 9th, 2021