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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.", "ID": "doi:10.1101/2021.02.09.430314", "@id": "/publications/14aefcd7-cec0-49b5-904f-851a9a1466f8/", "display_title": "Zazhytska M et al. (2021) doi:10.1101/2021.02.09.430314", "uuid": "14aefcd7-cec0-49b5-904f-851a9a1466f8", "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"], "journal": "bioRxiv : the preprint server for biology", "status": "current", "@type": ["Publication", "Item"], "url": "https://www.ncbi.nlm.nih.gov/pubmed/33594368", "title": "Disruption of nuclear architecture as a cause of COVID-19 induced anosmia.", "short_attribution": "Zazhytska M et al. (2021)", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"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.", "@type": ["Publication", "Item"], "journal": "bioRxiv : the preprint server for biology", "title": "Disruption of nuclear architecture as a cause of COVID-19 induced anosmia.", "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"], "ID": "doi:10.1101/2021.02.09.430314", "@id": "/publications/14aefcd7-cec0-49b5-904f-851a9a1466f8/", "date_published": "2021-02-09", "uuid": "14aefcd7-cec0-49b5-904f-851a9a1466f8", "display_title": "Zazhytska M et al. (2021) doi:10.1101/2021.02.09.430314", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 3, "@context": "/terms/", "aggregated-items": {"badges": []}, "validation-errors": []}