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

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.

Authors

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

Link

https://www.ncbi.nlm.nih.gov/pubmed/35180380