Disruption of nuclear architecture as a cause of COVID-19 induced anosmia.

Autor: Zazhytska M; Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY 10027, USA., Kodra A; Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY 10027, USA.; Department of Genetics and Development, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Hoagland DA; Department of Microbiology, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA., Fullard JF; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA.; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA., Shayya H; Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY 10027, USA.; Department of Genetics and Development, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Omer A; Baylor Genetics, 2450 Holcombe Blvd, Houston, TX, 77021, USA., Firestein S; Department of Biological Sciences, Columbia University New York, NY, 10027, USA., Gong Q; Department of Cell Biology and Human Anatomy, School of Medicine, University of California at Davis, Davis, CA 95616, USA., Canoll PD; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Goldman JE; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Roussos P; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA.; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA.; Department of Psychiatry, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA., tenOever BR; Department of Microbiology, Icahn School of Medicine at Mt. Sinai, New York, NY, 10029, USA., Overdevest JB; Department of Otolaryngology- Head and Neck Surgery, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA., Lomvardas S; Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY 10027, USA.; Department of Genetics and Development, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2021 Feb 09. Date of Electronic Publication: 2021 Feb 09.
DOI: 10.1101/2021.02.09.430314
Abstrakt: 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.
Databáze: MEDLINE