Molecular Medicine Israel

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

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 (OR)
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 SARSCoV-2 infection alters the cellular morphology and the transcriptome of cells it cannot infect,
offering insight to its systemic effects in olfaction and beyond….

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