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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.<\/jats:p>","DOI":"10.1101\/2021.02.09.430314","type":"posted-content","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:01:03Z","timestamp":1612915263000},"source":"Crossref","is-referenced-by-count":20,"title":["Disruption of nuclear architecture as a cause of COVID-19 induced anosmia"],"prefix":"10.64898","author":[{"given":"Marianna","family":"Zazhytska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albana","family":"Kodra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy A.","family":"Hoagland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Fullard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"Shayya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arina","family":"Omer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Firestein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qizhi","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Canoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Goldman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panos","family":"Roussos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin R.","family":"tenOever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B.","family":"Overdevest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavros","family":"Lomvardas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024080510152663000_2021.02.09.430314v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa525"},{"key":"2024080510152663000_2021.02.09.430314v1.2","doi-asserted-by":"publisher","DOI":"10.1177\/0194599820926473"},{"key":"2024080510152663000_2021.02.09.430314v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.05.017"},{"key":"2024080510152663000_2021.02.09.430314v1.4","doi-asserted-by":"publisher","DOI":"10.1101\/2020.07.22.20157263"},{"key":"2024080510152663000_2021.02.09.430314v1.5","doi-asserted-by":"publisher","DOI":"10.1177\/1073858420956905"},{"key":"2024080510152663000_2021.02.09.430314v1.6","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.0c00210"},{"key":"2024080510152663000_2021.02.09.430314v1.7","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01948-2020"},{"key":"2024080510152663000_2021.02.09.430314v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc5801"},{"key":"2024080510152663000_2021.02.09.430314v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.06.032"},{"key":"2024080510152663000_2021.02.09.430314v1.10","doi-asserted-by":"publisher","DOI":"10.1101\/2020.07.06.20147751"},{"key":"2024080510152663000_2021.02.09.430314v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00060-X"},{"key":"2024080510152663000_2021.02.09.430314v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80200-7"},{"key":"2024080510152663000_2021.02.09.430314v1.13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5563-12.2013"},{"key":"2024080510152663000_2021.02.09.430314v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.021"},{"key":"2024080510152663000_2021.02.09.430314v1.15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4948-12.2013"},{"key":"2024080510152663000_2021.02.09.430314v1.16","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4507-09.2010"},{"key":"2024080510152663000_2021.02.09.430314v1.17","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2010.24.3460"},{"key":"2024080510152663000_2021.02.09.430314v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.08.011"},{"key":"2024080510152663000_2021.02.09.430314v1.19","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15143"},{"key":"2024080510152663000_2021.02.09.430314v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2342-5"},{"key":"2024080510152663000_2021.02.09.430314v1.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2009799117"},{"key":"2024080510152663000_2021.02.09.430314v1.22","doi-asserted-by":"crossref","unstructured":"Daisy A. 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