Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers.
Aged
Aged, 80 and over
Angiotensin-Converting Enzyme 2
/ genetics
COVID-19
/ genetics
Female
Gene Expression Regulation
Humans
Male
Middle Aged
Nasal Cavity
/ metabolism
Respiratory Mucosa
/ metabolism
SARS-CoV-2
/ physiology
Serine Endopeptidases
/ genetics
Smokers
Trachea
/ metabolism
Viral Tropism
ACE2
COVID-19
IFN-β1
SARS-CoV-2
TMPRSS2
ciliated epithelial cell
nasal cavity
smoking
trachea
upper airway
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
19 10 2021
19 10 2021
Historique:
received:
05
02
2021
revised:
21
07
2021
accepted:
22
09
2021
pubmed:
5
10
2021
medline:
5
10
2021
entrez:
4
10
2021
Statut:
ppublish
Résumé
Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers.
Identifiants
pubmed: 34604819
doi: 10.1016/j.xcrm.2021.100421
pii: S2666-3791(21)00283-4
pmc: PMC8479532
doi:
Substances chimiques
ACE2 protein, human
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
Pagination
100421Subventions
Organisme : NIAID NIH HHS
ID : R01 AI149672
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151677
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209971
Pays : United States
Informations de copyright
© 2021.
Déclaration de conflit d'intérêts
I.T.L. is currently an employee and shareholder of Moderna, although this work was conducted prior to/independent of his employment. I.T.L. had also received research support unrelated to this study from Genentech (Roche). Moderna did not fund or participate in this study in any form.
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