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

Zazhytska M, Kodra A, Hoagland DA, Frere J, Fullard JF, Shayya H, McArthur NG, Moeller R, Uhl S, Omer AD, Gottesman ME, Firestein S, Gong Q, Canoll PD, Goldman JE, Roussos P, tenOever BR, Jonathan B Overdevest, Lomvardas S

10.1016/j.cell.2022.01.024 02/02/2022

PMID: 35180380

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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.

Keywords: COVID-19; anosmia; nuclear architecture.