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

Marianna Zazhytska; Albana Kodra; Daisy A Hoagland; Justin Frere; John F Fullard; Hani Shayya; Natalie G McArthur; Rasmus Moeller; Skyler Uhl; Arina D Omer; Max E Gottesman; Stuart Firestein; Qizhi Gong; Peter D Canoll; James E Goldman; Panos Roussos; Benjamin R tenOever; Jonathan B Overdevest; Stavros Lomvardas

doi:10.1016/j.cell.2022.01.024

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

Cell. 2022 Mar 17;185(6):1052-1064.e12. doi: 10.1016/j.cell.2022.01.024. Epub 2022 Feb 2.

Authors

Marianna Zazhytska¹, Albana Kodra², Daisy A Hoagland³, Justin Frere³, John F Fullard⁴, Hani Shayya², Natalie G McArthur⁵, Rasmus Moeller³, Skyler Uhl³, Arina D Omer⁶, Max E Gottesman⁷, Stuart Firestein⁵, Qizhi Gong⁸, Peter D Canoll⁹, James E Goldman⁹, Panos Roussos¹⁰, Benjamin R tenOever¹¹, Jonathan B Overdevest¹², Stavros Lomvardas¹³

Affiliations

¹ Mortimer B. Zuckerman Mind, and Brain and Behavior Institute, Columbia University, New York, NY 10027, USA.
² Mortimer B. Zuckerman Mind, and 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.
³ Department of Microbiology, Icahn School of Medicine at Mt. Sinai, New York, NY 10029, USA.
⁴ Center for Disease Neurogenomics, 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.
⁵ Department of Biological Sciences, Columbia University New York, NY 10027, USA.
⁶ Baylor Genetics, 2450 Holcombe Blvd, Houston, TX 77021, USA.
⁷ Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
⁸ Department of Cell Biology and Human Anatomy, School of Medicine, University of California at Davis, Davis, CA 95616, USA.
⁹ Department of Pathology and Cell Biology, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
¹⁰ Center for Disease Neurogenomics, 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.
¹¹ Department of Microbiology, Icahn School of Medicine at Mt. Sinai, New York, NY 10029, USA. Electronic address: benjamin.tenoever@nyulangone.edu.
¹² 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. Electronic address: jo2566@cumc.columbia.edu.
¹³ Mortimer B. Zuckerman Mind, and Brain and Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: sl682@cumc.columbia.edu.

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.

Keywords: COVID-19; anosmia; nuclear architecture.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anosmia*
COVID-19*
Cricetinae
Down-Regulation
Humans
Receptors, Odorant
SARS-CoV-2
Smell

Substances

Receptors, Odorant

Abstract

Publication types

MeSH terms

Substances

Grants and funding