SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants

Lisiena Hysenaj; Samantha Little; Kayla Kulhanek; Melia Magnen; Kriti Bahl; Oghenekevwe M. Gbenedio; Morgan Prinz; Lauren Rodriguez; Christopher Andersen; Arjun Arkal Rao; Alan Shen; Jean Christophe Lone; Leonard C. Lupin-Jimenez; Luke R. Bonser; Nina K. Serwas; Eran Mick; Mir M. Khalid; Taha Y. Taha; Renuka Kumar; Jack Z. Li; Vivianne W. Ding; Shotaro Matsumoto; Mazharul Maishan; Bharath Sreekumar; Camille Simoneau; Irina Nazarenko; Michael G. Tomlinson; Khajida Khan; Anne von Gottberg; Alex Sigal; Mark R. Looney; Gabriela K. Fragiadakis; David M. Jablons; Charles R. Langelier; Michael Matthay; Matthew Krummel; David J. Erle; Alexis J. Combes; Anita Sil; Melanie Ott; Johannes R. Kratz; Jeroen P. Roose

doi:10.1016/j.stemcr.2023.01.011

SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants

Lisiena Hysenaj, Samantha Little, Kayla Kulhanek, Melia Magnen, Kriti Bahl, Oghenekevwe M. Gbenedio, Morgan Prinz, Lauren Rodriguez, Christopher Andersen, Arjun Arkal Rao, Alan Shen, Jean Christophe Lone, Leonard C. Lupin-Jimenez, Luke R. Bonser, Nina K. Serwas, Eran Mick, Mir M. Khalid, Taha Y. Taha, Renuka Kumar, Jack Z. LiVivianne W. Ding, Shotaro Matsumoto, Mazharul Maishan, Bharath Sreekumar, Camille Simoneau, Irina Nazarenko, Michael G. Tomlinson, Khajida Khan, Anne von Gottberg, Alex Sigal, Mark R. Looney, Gabriela K. Fragiadakis, David M. Jablons, Charles R. Langelier, Michael Matthay, Matthew Krummel, David J. Erle, Alexis J. Combes, Anita Sil, Melanie Ott, Johannes R. Kratz, Jeroen P. Roose^*

^*Corresponding author for this work

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

10 Scopus citations

Abstract

Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease severity. The mechanistic explaining variations related to airway epithelium are relatively understudied. Here, we biobanked airway organoids (AO) by preserving stem cell function. We optimized viral infection with H1N1/PR8 and comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable AO from 20 different subjects. We discovered Tetraspanin-8 (TSPAN8) as a facilitator of SARS-CoV-2 infection. TSPAN8 facilitates SARS-CoV-2 infection rates independently of ACE2-Spike interaction. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta and Omicron VOC displayed lower overall infection rates of AO but triggered changes in epithelial response. All variants shared highest tropism for ciliated and goblet cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.

Original language	English
Pages (from-to)	636-653
Number of pages	18
Journal	Stem Cell Reports
Volume	18
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2023.01.011
State	Published - 14 Mar 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

H1N1
SARS-CoV-2
TSPAN8
airway organoids
cell composition
single cell RNAseq
spectral flow
therapeutics
variants
virus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.stemcr.2023.01.011

Cite this

Hysenaj, L., Little, S., Kulhanek, K., Magnen, M., Bahl, K., Gbenedio, O. M., Prinz, M., Rodriguez, L., Andersen, C., Rao, A. A., Shen, A., Lone, J. C., Lupin-Jimenez, L. C., Bonser, L. R., Serwas, N. K., Mick, E., Khalid, M. M., Taha, T. Y., Kumar, R., ... Roose, J. P. (2023). SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants. Stem Cell Reports, 18(3), 636-653. https://doi.org/10.1016/j.stemcr.2023.01.011

@article{c89369db377d4fa9b571114fcbb6dc0d,

title = "SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants",

abstract = "Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease severity. The mechanistic explaining variations related to airway epithelium are relatively understudied. Here, we biobanked airway organoids (AO) by preserving stem cell function. We optimized viral infection with H1N1/PR8 and comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable AO from 20 different subjects. We discovered Tetraspanin-8 (TSPAN8) as a facilitator of SARS-CoV-2 infection. TSPAN8 facilitates SARS-CoV-2 infection rates independently of ACE2-Spike interaction. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta and Omicron VOC displayed lower overall infection rates of AO but triggered changes in epithelial response. All variants shared highest tropism for ciliated and goblet cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.",

keywords = "H1N1, SARS-CoV-2, TSPAN8, airway organoids, cell composition, single cell RNAseq, spectral flow, therapeutics, variants, virus",

author = "Lisiena Hysenaj and Samantha Little and Kayla Kulhanek and Melia Magnen and Kriti Bahl and Gbenedio, \{Oghenekevwe M.\} and Morgan Prinz and Lauren Rodriguez and Christopher Andersen and Rao, \{Arjun Arkal\} and Alan Shen and Lone, \{Jean Christophe\} and Lupin-Jimenez, \{Leonard C.\} and Bonser, \{Luke R.\} and Serwas, \{Nina K.\} and Eran Mick and Khalid, \{Mir M.\} and Taha, \{Taha Y.\} and Renuka Kumar and Li, \{Jack Z.\} and Ding, \{Vivianne W.\} and Shotaro Matsumoto and Mazharul Maishan and Bharath Sreekumar and Camille Simoneau and Irina Nazarenko and Tomlinson, \{Michael G.\} and Khajida Khan and \{von Gottberg\}, Anne and Alex Sigal and Looney, \{Mark R.\} and Fragiadakis, \{Gabriela K.\} and Jablons, \{David M.\} and Langelier, \{Charles R.\} and Michael Matthay and Matthew Krummel and Erle, \{David J.\} and Combes, \{Alexis J.\} and Anita Sil and Melanie Ott and Kratz, \{Johannes R.\} and Roose, \{Jeroen P.\}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = mar,

day = "14",

doi = "10.1016/j.stemcr.2023.01.011",

language = "אנגלית",

volume = "18",

pages = "636--653",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

number = "3",

}

Hysenaj, L, Little, S, Kulhanek, K, Magnen, M, Bahl, K, Gbenedio, OM, Prinz, M, Rodriguez, L, Andersen, C, Rao, AA, Shen, A, Lone, JC, Lupin-Jimenez, LC, Bonser, LR, Serwas, NK, Mick, E, Khalid, MM, Taha, TY, Kumar, R, Li, JZ, Ding, VW, Matsumoto, S, Maishan, M, Sreekumar, B, Simoneau, C, Nazarenko, I, Tomlinson, MG, Khan, K, von Gottberg, A, Sigal, A, Looney, MR, Fragiadakis, GK, Jablons, DM, Langelier, CR, Matthay, M, Krummel, M, Erle, DJ, Combes, AJ, Sil, A, Ott, M, Kratz, JR & Roose, JP 2023, 'SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants', Stem Cell Reports, vol. 18, no. 3, pp. 636-653. https://doi.org/10.1016/j.stemcr.2023.01.011

TY - JOUR

T1 - SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants

AU - Hysenaj, Lisiena

AU - Little, Samantha

AU - Kulhanek, Kayla

AU - Magnen, Melia

AU - Bahl, Kriti

AU - Gbenedio, Oghenekevwe M.

AU - Prinz, Morgan

AU - Rodriguez, Lauren

AU - Andersen, Christopher

AU - Rao, Arjun Arkal

AU - Shen, Alan

AU - Lone, Jean Christophe

AU - Lupin-Jimenez, Leonard C.

AU - Bonser, Luke R.

AU - Serwas, Nina K.

AU - Mick, Eran

AU - Khalid, Mir M.

AU - Taha, Taha Y.

AU - Kumar, Renuka

AU - Li, Jack Z.

AU - Ding, Vivianne W.

AU - Matsumoto, Shotaro

AU - Maishan, Mazharul

AU - Sreekumar, Bharath

AU - Simoneau, Camille

AU - Nazarenko, Irina

AU - Tomlinson, Michael G.

AU - Khan, Khajida

AU - von Gottberg, Anne

AU - Sigal, Alex

AU - Looney, Mark R.

AU - Fragiadakis, Gabriela K.

AU - Jablons, David M.

AU - Langelier, Charles R.

AU - Matthay, Michael

AU - Krummel, Matthew

AU - Erle, David J.

AU - Combes, Alexis J.

AU - Sil, Anita

AU - Ott, Melanie

AU - Kratz, Johannes R.

AU - Roose, Jeroen P.

PY - 2023/3/14

Y1 - 2023/3/14

N2 - Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease severity. The mechanistic explaining variations related to airway epithelium are relatively understudied. Here, we biobanked airway organoids (AO) by preserving stem cell function. We optimized viral infection with H1N1/PR8 and comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable AO from 20 different subjects. We discovered Tetraspanin-8 (TSPAN8) as a facilitator of SARS-CoV-2 infection. TSPAN8 facilitates SARS-CoV-2 infection rates independently of ACE2-Spike interaction. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta and Omicron VOC displayed lower overall infection rates of AO but triggered changes in epithelial response. All variants shared highest tropism for ciliated and goblet cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.

AB - Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease severity. The mechanistic explaining variations related to airway epithelium are relatively understudied. Here, we biobanked airway organoids (AO) by preserving stem cell function. We optimized viral infection with H1N1/PR8 and comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable AO from 20 different subjects. We discovered Tetraspanin-8 (TSPAN8) as a facilitator of SARS-CoV-2 infection. TSPAN8 facilitates SARS-CoV-2 infection rates independently of ACE2-Spike interaction. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta and Omicron VOC displayed lower overall infection rates of AO but triggered changes in epithelial response. All variants shared highest tropism for ciliated and goblet cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.

KW - H1N1

KW - SARS-CoV-2

KW - TSPAN8

KW - airway organoids

KW - cell composition

KW - single cell RNAseq

KW - spectral flow

KW - therapeutics

KW - variants

KW - virus

UR - https://www.scopus.com/pages/publications/85149930838

U2 - 10.1016/j.stemcr.2023.01.011

DO - 10.1016/j.stemcr.2023.01.011

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 36827975

AN - SCOPUS:85149930838

SN - 2213-6711

VL - 18

SP - 636

EP - 653

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 3

ER -

SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this