1. Publications

Non-cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19-induced anosmia

Marianna Zazhytska, Albana Kodra, Daisy A Hoagland, Justin Frere, John F Fullard, Hani Shayya, Natalie G McArthur, Rasmus Moeller, Skyler Uhl, Arina D Omer, Max E Gottesman, Stuart Firestein, Qizhi Gong, Peter D Canoll, James E Goldman, Panos Roussos, Benjamin R tenOever, Jonathan B Overdevest, Stavros Lomvardas.
Cell. 2022-03-17;185(6):1052-1064.e12.
Abstract
SARS-CoV-2 infects less than 1% of cells in the human body, yet it can cause severe damage in a variety of organs. Thus, deciphering the non-cell-autonomous effects of SARS-CoV-2 infection is imperative for understanding the cellular and molecular disruption it elicits. Neurological and cognitive defects are among the least understood symptoms of COVID-19 patients, with olfactory dysfunction being their most common sensory deficit. Here, we show that both in humans and hamsters, SARS-CoV-2 infection causes widespread downregulation of olfactory receptors (ORs) and of their signaling components. This non-cell-autonomous effect is preceded by a dramatic reorganization of the neuronal nuclear architecture, which results in dissipation of genomic compartments harboring OR genes. Our data provide a potential mechanism by which SARS-CoV-2 infection alters the cellular morphology and the transcriptome of cells it cannot infect, offering insight to its systemic effects in olfaction and beyond.

Related data

Available data
website
Data summary
Human and hamster RNAseq, scRNAseq, in situ HiC, supplemental spreadsheets and detailed experimental protocols have been deposited to 4DN portal.
Data summary
This study did not generate custom computer code. Any additional information is available from the Lead Contact upon request.