Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia.
Angiotensin-Converting Enzyme 2
Animals
Betacoronavirus
/ physiology
COVID-19
Callithrix
Coronavirus Infections
/ pathology
Humans
Macaca
Mice
Olfaction Disorders
/ genetics
Olfactory Mucosa
/ cytology
Olfactory Receptor Neurons
/ metabolism
Pandemics
Peptidyl-Dipeptidase A
/ genetics
Pneumonia, Viral
/ pathology
SARS-CoV-2
Serine Endopeptidases
/ genetics
Smell
/ genetics
Virus Internalization
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
31 07 2020
31 07 2020
Historique:
received:
01
05
2020
accepted:
18
06
2020
entrez:
16
9
2020
pubmed:
17
9
2020
medline:
29
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32937591
pii: sciadv.abc5801
doi: 10.1126/sciadv.abc5801
pmc: PMC10715684
pii:
doi:
Substances chimiques
Peptidyl-Dipeptidase A
EC 3.4.15.1
ACE2 protein, human
EC 3.4.17.23
Ace2 protein, mouse
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC014423
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC016222
Pays : United States
Organisme : NIH HHS
ID : R011DC016222
Pays : United States
Organisme : NIDCD NIH HHS
ID : F31 DC019017
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC016224
Pays : United States
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : NIDCD NIH HHS
ID : R01 DC007235
Pays : United States
Organisme : NINDS NIH HHS
ID : U19 NS112953
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC016859
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS072030
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
Références
Nat Commun. 2015 Oct 15;6:8557
pubmed: 26469390
J Virol. 2011 Dec;85(24):13363-72
pubmed: 21994442
J Physiol. 2005 Feb 1;562(Pt 3):785-99
pubmed: 15611020
JAMA. 2020 Apr 7;323(13):1239-1242
pubmed: 32091533
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Elife. 2018 Apr 20;7:
pubmed: 29676260
Clin Infect Dis. 2020 Jul 28;71(15):889-890
pubmed: 32215618
N Engl J Med. 2020 Aug 6;383(6):590-592
pubmed: 32402155
J Infect Dis. 2005 Mar 1;191(5):755-60
pubmed: 15688292
Nucleic Acids Res. 1999 Nov 15;27(22):4324-7
pubmed: 10536138
Cell. 2015 May 21;161(5):1202-1214
pubmed: 26000488
Front Neurol. 2021 Jan 20;11:573095
pubmed: 33551947
J Comp Neurol. 2015 Feb 15;523(3):406-30
pubmed: 25271146
iScience. 2020 Dec 18;23(12):101839
pubmed: 33251489
N Engl J Med. 2020 Feb 20;382(8):727-733
pubmed: 31978945
PLoS Comput Biol. 2018 Sep 4;14(9):e1006378
pubmed: 30180157
Am J Respir Crit Care Med. 2020 Dec 15;202(12):1636-1645
pubmed: 32726565
J Korean Med Sci. 2020 May 11;35(18):e174
pubmed: 32383370
J Virol. 2004 Sep;78(18):10156-65
pubmed: 15331748
Nat Med. 2019 Jul;25(7):1153-1163
pubmed: 31209336
Neurology. 2020 Aug 4;95(5):224-225
pubmed: 32444492
Nat Neurosci. 2018 Jun;21(6):869-880
pubmed: 29686262
Sci Rep. 2015 Dec 16;5:18178
pubmed: 26670777
J Otolaryngol Head Neck Surg. 2020 May 4;49(1):26
pubmed: 32366299
Bioinformatics. 2018 Apr 1;34(7):1246-1248
pubmed: 29228172
Neuron. 2014 Aug 20;83(4):823-38
pubmed: 25123312
JAMA. 2020 May 26;323(20):2089-2090
pubmed: 32320008
Gigascience. 2018 Jul 1;7(7):
pubmed: 30010766
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
Cell. 2018 Aug 9;174(4):999-1014.e22
pubmed: 30096314
Eur Respir J. 2020 Sep 24;56(3):
pubmed: 32817004
Radiology. 2020 Aug;296(2):E119-E120
pubmed: 32228363
JAMA Neurol. 2020 Aug 1;77(8):1028-1029
pubmed: 32469400
J Virol. 2008 Aug;82(15):7264-75
pubmed: 18495771
Front Cell Neurosci. 2018 Oct 26;12:386
pubmed: 30416428
Cell Syst. 2019 Apr 24;8(4):315-328.e8
pubmed: 31022373
Neuron. 2010 Nov 18;68(4):682-94
pubmed: 21092858
Eur Arch Otorhinolaryngol. 2020 Aug;277(8):2251-2261
pubmed: 32253535
Nat Biotechnol. 2016 May;34(5):525-7
pubmed: 27043002
Nat Rev Drug Discov. 2016 May;15(5):327-47
pubmed: 26868298
Chem Senses. 2001 Oct;26(8):953-63
pubmed: 11595672
Nature. 2003 Nov 27;426(6965):450-4
pubmed: 14647384
Biol Open. 2018 Nov 19;7(11):
pubmed: 30455179
Adv Virus Res. 2018;100:163-188
pubmed: 29551135
J Neurol Neurosurg Psychiatry. 2020 Aug;91(8):889-891
pubmed: 32354768
Genome Biol. 2018 Feb 6;19(1):15
pubmed: 29409532
Virology. 1993 May;194(1):185-91
pubmed: 8386871
Cell Host Microbe. 2020 Jul 8;28(1):124-133.e4
pubmed: 32485164
Elife. 2020 Jul 07;9:
pubmed: 32633720
ACS Chem Neurosci. 2020 Jun 3;11(11):1555-1562
pubmed: 32379417
Cell. 2020 May 28;181(5):1016-1035.e19
pubmed: 32413319
Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R373-81
pubmed: 16946085
Neurology. 2020 Oct 6;95(14):e2016-e2027
pubmed: 32546654
Handb Clin Neurol. 2019;164:361-387
pubmed: 31604558
Cell. 2020 Jul 23;182(2):429-446.e14
pubmed: 32526206
Nat Commun. 2020 Oct 12;11(1):5139
pubmed: 33046696
Nature. 2020 May;581(7809):465-469
pubmed: 32235945
Cell. 2016 Oct 6;167(2):566-580.e19
pubmed: 27716510
J Biol Chem. 2018 Jul 27;293(30):11709-11726
pubmed: 29887526
Cell. 2018 Aug 23;174(5):1229-1246.e17
pubmed: 30078709
PLoS One. 2015 Jan 15;10(1):e0113170
pubmed: 25590618
ORL J Otorhinolaryngol Relat Spec. 2020;82(4):175-180
pubmed: 32526759
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Alzheimers Res Ther. 2016 Nov 25;8(1):50
pubmed: 27884212
JAMA. 2020 Jun 23;323(24):2518-2520
pubmed: 32437497
Nat Neurosci. 2020 Mar;23(3):323-326
pubmed: 32066986
Chem Senses. 2020 Oct 9;45(7):609-622
pubmed: 32564071
Cell Stem Cell. 2019 Oct 3;25(4):501-513.e5
pubmed: 31523027
J Pathol. 2004 Jun;203(2):631-7
pubmed: 15141377
Cell. 2018 May 17;173(5):1280-1292.e18
pubmed: 29681453
Arch Otolaryngol Head Neck Surg. 1995 Oct;121(10):1183-7
pubmed: 7546588
Sci Adv. 2019 Jul 31;5(7):eaax0396
pubmed: 31392275
Laryngoscope. 2018 Jan;128(1):10-15
pubmed: 28556265
Nature. 2018 Aug;560(7718):377-381
pubmed: 30069046
Nat Protoc. 2016 Nov;11(11):2081-103
pubmed: 27685099
Int Forum Allergy Rhinol. 2020 Jul;10(7):814-820
pubmed: 32271490
Cell. 2016 Aug 25;166(5):1308-1323.e30
pubmed: 27565351
Science. 2020 Feb 14;367(6479):
pubmed: 31974159
Environ Health Perspect. 1990 Apr;85:171-6
pubmed: 2384061
Int Forum Allergy Rhinol. 2020 Jul;10(7):806-813
pubmed: 32279441
BMJ. 2020 Mar 26;368:m1091
pubmed: 32217556
N Engl J Med. 2020 Jun 4;382(23):2268-2270
pubmed: 32294339
J Autoimmun. 2020 May;109:102433
pubmed: 32113704
Cell Stem Cell. 2017 Dec 7;21(6):775-790.e9
pubmed: 29174333
Cell Syst. 2019 Apr 24;8(4):281-291.e9
pubmed: 30954476
Cell. 2020 Jul 9;182(1):50-58.e8
pubmed: 32516571
PLoS One. 2012;7(4):e35876
pubmed: 22558251
Med J Islam Repub Iran. 2020 Jun 15;34:62
pubmed: 32974228
Nature. 2020 Jul;583(7818):830-833
pubmed: 32380511
Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2781-2783
pubmed: 32196628
Bioinformatics. 2017 Apr 15;33(8):1179-1186
pubmed: 28088763
Cell Syst. 2019 Apr 24;8(4):329-337.e4
pubmed: 30954475
Cell Rep. 2018 Jan 9;22(2):441-455
pubmed: 29320739
Adv Otorhinolaryngol. 2006;63:125-132
pubmed: 16733337
Genome Biol. 2016 Apr 27;17:75
pubmed: 27122128
Exp Neurol. 1995 Dec;136(2):225-33
pubmed: 7498412
Laryngoscope Investig Otolaryngol. 2018 Feb 06;3(1):35-42
pubmed: 29492466
Nat Neurosci. 2016 Oct;19(10):1331-40
pubmed: 27571008
BMC Dev Biol. 2001;1:4
pubmed: 11299042
Cell Stem Cell. 2017 Jun 1;20(6):817-830.e8
pubmed: 28506465
Vet Pathol. 1995 Jan;32(1):1-10
pubmed: 7725592
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
J Comp Neurol. 1996 Dec 23;376(4):509-17
pubmed: 8978466
Nat Med. 2020 Jul;26(7):1037-1040
pubmed: 32393804
Nat Neurosci. 2015 Jan;18(1):145-53
pubmed: 25420068
Nat Med. 2005 Aug;11(8):875-9
pubmed: 16007097
J Intern Med. 2020 Sep;288(3):335-344
pubmed: 32352202
N Engl J Med. 2020 Apr 23;382(17):e38
pubmed: 32268022
Nature. 2020 Sep;585(7824):268-272
pubmed: 32396922
Nat Neurosci. 2017 Feb;20(2):176-188
pubmed: 27991900
Nat Protoc. 2007;2(11):2924-9
pubmed: 18007629
Nat Biotechnol. 2014 Sep;32(9):896-902
pubmed: 25150836
Science. 2020 Jul 3;369(6499):50-54
pubmed: 32358202
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
J Comp Neurol. 2017 Mar 1;525(4):1034-1054
pubmed: 27560601
Front Cell Neurosci. 2019 Jun 28;13:282
pubmed: 31316352
Nat Med. 2020 May;26(5):681-687
pubmed: 32327758
JAMA Otolaryngol Head Neck Surg. 2020 Jul 1;146(7):674-675
pubmed: 32267483
J Virol. 2004 Oct;78(20):11429-33
pubmed: 15452268
Chem Senses. 2001 Oct;26(8):937-52
pubmed: 11595671