Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers

Tsuguhisa Nakayama; Ivan T. Lee; Sizun Jiang; Matthias S. Matter; Carol H. Yan; Jonathan B. Overdevest; Chien Ting Wu; Yury Goltsev; Liang Chun Shih; Chun Kang Liao; Bokai Zhu; Yunhao Bai; Peter Lidsky; Yinghong Xiao; David Zarabanda; Angela Yang; Meena Easwaran; Christian M. Schürch; Pauline Chu; Han Chen; Anna K. Stalder; David R. McIlwain; Nicole A. Borchard; Phillip A. Gall; Sachi S. Dholakia; Wei Le; Le Xu; Chih Jaan Tai; Te Huei Yeh; Elizabeth Erickson-Direnzo; Jason M. Duran; Kirsten D. Mertz; Peter H. Hwang; Jasmin D. Haslbauer; Peter K. Jackson; Thomas Menter; Raul Andino; Peter D. Canoll; Adam S. DeConde; Zara M. Patel; Alexandar Tzankov; Garry P. Nolan; Jayakar V. Nayak

doi:10.1016/j.xcrm.2021.100421

Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers

Tsuguhisa Nakayama, Ivan T. Lee, Sizun Jiang, Matthias S. Matter, Carol H. Yan, Jonathan B. Overdevest, Chien Ting Wu, Yury Goltsev, Liang Chun Shih, Chun Kang Liao, Bokai Zhu, Yunhao Bai, Peter Lidsky, Yinghong Xiao, David Zarabanda, Angela Yang, Meena Easwaran, Christian M. Schürch, Pauline Chu, Han ChenAnna K. Stalder, David R. McIlwain, Nicole A. Borchard, Phillip A. Gall, Sachi S. Dholakia, Wei Le, Le Xu, Chih Jaan Tai, Te Huei Yeh, Elizabeth Erickson-Direnzo, Jason M. Duran, Kirsten D. Mertz, Peter H. Hwang, Jasmin D. Haslbauer, Peter K. Jackson, Thomas Menter, Raul Andino, Peter D. Canoll, Adam S. DeConde, Zara M. Patel, Alexandar Tzankov, Garry P. Nolan, Jayakar V. Nayak

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

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.

Original language	English (US)
Article number	100421
Journal	Cell Reports Medicine
Volume	2
Issue number	10
DOIs	https://doi.org/10.1016/j.xcrm.2021.100421
State	Published - Oct 19 2021
Externally published	Yes

Keywords

ACE2
COVID-19
IFN-β1
SARS-CoV-2
TMPRSS2
ciliated epithelial cell
nasal cavity
smoking
trachea
upper airway

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2021.100421

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Nakayama, T., Lee, I. T., Jiang, S., Matter, M. S., Yan, C. H., Overdevest, J. B., Wu, C. T., Goltsev, Y., Shih, L. C., Liao, C. K., Zhu, B., Bai, Y., Lidsky, P., Xiao, Y., Zarabanda, D., Yang, A., Easwaran, M., Schürch, C. M., Chu, P., ... Nayak, J. V. (2021). Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers. Cell Reports Medicine, 2(10), Article 100421. https://doi.org/10.1016/j.xcrm.2021.100421

Nakayama, T, Lee, IT, Jiang, S, Matter, MS, Yan, CH, Overdevest, JB, Wu, CT, Goltsev, Y, Shih, LC, Liao, CK, Zhu, B, Bai, Y, Lidsky, P, Xiao, Y, Zarabanda, D, Yang, A, Easwaran, M, Schürch, CM, Chu, P, Chen, H, Stalder, AK, McIlwain, DR, Borchard, NA, Gall, PA, Dholakia, SS, Le, W, Xu, L, Tai, CJ, Yeh, TH, Erickson-Direnzo, E, Duran, JM, Mertz, KD, Hwang, PH, Haslbauer, JD, Jackson, PK, Menter, T, Andino, R, Canoll, PD, DeConde, AS, Patel, ZM, Tzankov, A, Nolan, GP & Nayak, JV 2021, 'Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers', Cell Reports Medicine, vol. 2, no. 10, 100421. https://doi.org/10.1016/j.xcrm.2021.100421

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title = "Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers",

abstract = "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.",

keywords = "ACE2, COVID-19, IFN-β1, SARS-CoV-2, TMPRSS2, ciliated epithelial cell, nasal cavity, smoking, trachea, upper airway",

author = "Tsuguhisa Nakayama and Lee, {Ivan T.} and Sizun Jiang and Matter, {Matthias S.} and Yan, {Carol H.} and Overdevest, {Jonathan B.} and Wu, {Chien Ting} and Yury Goltsev and Shih, {Liang Chun} and Liao, {Chun Kang} and Bokai Zhu and Yunhao Bai and Peter Lidsky and Yinghong Xiao and David Zarabanda and Angela Yang and Meena Easwaran and Sch{\"u}rch, {Christian M.} and Pauline Chu and Han Chen and Stalder, {Anna K.} and McIlwain, {David R.} and Borchard, {Nicole A.} and Gall, {Phillip A.} and Dholakia, {Sachi S.} and Wei Le and Le Xu and Tai, {Chih Jaan} and Yeh, {Te Huei} and Elizabeth Erickson-Direnzo and Duran, {Jason M.} and Mertz, {Kirsten D.} and Hwang, {Peter H.} and Haslbauer, {Jasmin D.} and Jackson, {Peter K.} and Thomas Menter and Raul Andino and Canoll, {Peter D.} and DeConde, {Adam S.} and Patel, {Zara M.} and Alexandar Tzankov and Nolan, {Garry P.} and Nayak, {Jayakar V.}",

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year = "2021",

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doi = "10.1016/j.xcrm.2021.100421",

language = "English (US)",

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AU - Nakayama, Tsuguhisa

AU - Lee, Ivan T.

AU - Jiang, Sizun

AU - Matter, Matthias S.

AU - Yan, Carol H.

AU - Overdevest, Jonathan B.

AU - Wu, Chien Ting

AU - Goltsev, Yury

AU - Shih, Liang Chun

AU - Liao, Chun Kang

AU - Zhu, Bokai

AU - Bai, Yunhao

AU - Lidsky, Peter

AU - Xiao, Yinghong

AU - Zarabanda, David

AU - Yang, Angela

AU - Easwaran, Meena

AU - Schürch, Christian M.

AU - Chu, Pauline

AU - Chen, Han

AU - Stalder, Anna K.

AU - McIlwain, David R.

AU - Borchard, Nicole A.

AU - Gall, Phillip A.

AU - Dholakia, Sachi S.

AU - Le, Wei

AU - Xu, Le

AU - Tai, Chih Jaan

AU - Yeh, Te Huei

AU - Erickson-Direnzo, Elizabeth

AU - Duran, Jason M.

AU - Mertz, Kirsten D.

AU - Hwang, Peter H.

AU - Haslbauer, Jasmin D.

AU - Jackson, Peter K.

AU - Menter, Thomas

AU - Andino, Raul

AU - Canoll, Peter D.

AU - DeConde, Adam S.

AU - Patel, Zara M.

AU - Tzankov, Alexandar

AU - Nolan, Garry P.

AU - Nayak, Jayakar V.

PY - 2021/10/19

Y1 - 2021/10/19

N2 - 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.

AB - 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.

KW - ACE2

KW - COVID-19

KW - IFN-β1

KW - SARS-CoV-2

KW - TMPRSS2

KW - ciliated epithelial cell

KW - nasal cavity

KW - smoking

KW - trachea

KW - upper airway

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DO - 10.1016/j.xcrm.2021.100421

M3 - Article

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AN - SCOPUS:85116801681

SN - 2666-3791

VL - 2

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 10

M1 - 100421

ER -

Determinants of SARS-CoV-2 entry and replication in airway mucosal tissue and susceptibility in smokers

Abstract

Keywords

ASJC Scopus subject areas

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