Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

Autor: Sandrine Dudoit, Rebecca K. Chance, Elizabeth Purdom, Darren W. Logan, Iain C. Macaulay, Boying Gong, Ralph Abi Hachem, Koen Van den Berge, Jonathan Mill, Hiroaki Matsunami, Tatsuya Tsukahara, Diya Das, Hector Roux de Bézieux, Davide Risso, Hsin-jung Chou, Caleb Weinreb, Russell B. Fletcher, Matthew S. Grubb, John Ngai, David H. Brann, Marcela Lipovsek, Sandeep Robert Datta, Bradley J. Goldstein, Kelly Street, Yoon Gi Choi
Jazyk: angličtina
Předmět:
Olfactory system
VARIANT
DIVERSITY
Mice
Olfaction Disorders
0302 clinical medicine
RESPIRATORY SYNDROME CORONAVIRUS
FUNCTIONAL RECEPTOR
Medicine and Health Sciences
NEURON
0303 health sciences
Multidisciplinary
Serine Endopeptidases
Callithrix
STEM
Smell
Mathematics and Statistics
medicine.anatomical_structure
Angiotensin-Converting Enzyme 2
medicine.symptom
Coronavirus Infections
Cell type
EPITHELIUM
Pneumonia
Viral

Anosmia
Sensory system
Olfaction
Peptidyl-Dipeptidase A
Biology
Olfactory Receptor Neurons
Betacoronavirus
03 medical and health sciences
Olfactory mucosa
Olfactory Mucosa
SARS CORONAVIRUS
medicine
Animals
Humans
Pandemics
030304 developmental biology
SARS-CoV-2
COVID-19
Virus Internalization
Olfactory bulb
nervous system
CELLS
Macaca
RNA-SEQ DATA
MOUSE HEPATITIS-VIRUS
Olfactory epithelium
Neuroscience
BULB LINE
030217 neurology & neurosurgery
Zdroj: Science Advances
Brann, D H, Tsukahara, T, Weinreb, C, Lipovsek, M, Van den Berge, K, Gong, B, Chance, R, Macaulay, I C, Chou, H J, Fletcher, R B, Das, D, Street, K, de Bezieux, H R, Choi, Y G, Risso, D, Dudoit, S, Purdom, E, Mill, J, Hachem, R A, Matsunami, H, Logan, D W, Goldstein, B J, Grubb, M S, Ngai, J & Datta, S R 2020, ' Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia ', Science Advances, vol. 6, no. 31, abc5801 . https://doi.org/10.1126/sciadv.abc5801
SCIENCE ADVANCES
ISSN: 2375-2548
DOI: 10.1126/sciadv.abc5801
Popis: Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.
Databáze: OpenAIRE