The use of human iPSC-derived alveolar organoids to explore SARS-CoV-2 variant infections and host responses
© 2024 Wiley Periodicals LLC..
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) primarily targets the respiratory system. Physiologically relevant human lung models are indispensable to investigate virus-induced host response and disease pathogenesis. In this study, we generated human induced pluripotent stem cell (iPSC)-derived alveolar organoids (AOs) using an established protocol that recapitulates the sequential steps of in vivo lung development. AOs express alveolar epithelial type II cell protein markers including pro-surfactant protein C and ATP binding cassette subfamily A member 3. Compared to primary human alveolar type II cells, AOs expressed higher mRNA levels of SARS-CoV-2 entry factors, angiotensin-converting enzyme 2 (ACE2), asialoglycoprotein receptor 1 (ASGR1) and basigin (CD147). Considering the localization of ACE2 on the apical side in AOs, we used three AO models, apical-in, sheared and apical-out for SARS-CoV-2 infection. All three models of AOs were robustly infected with the SARS-CoV-2 irrespective of ACE2 accessibility. Antibody blocking experiment revealed that ASGR1 was the main receptor for SARS-CoV2 entry from the basolateral in apical-in AOs. AOs supported the replication of SARS-CoV-2 variants WA1, Alpha, Beta, Delta, and Zeta and Omicron to a variable degree with WA1 being the highest and Omicron being the least. Transcriptomic profiling of infected AOs revealed the induction of inflammatory and interferon-related pathways with NF-κB signaling being the predominant host response. In summary, iPSC-derived AOs can serve as excellent human lung models to investigate infection of SARS-CoV-2 variants and host responses from both apical and basolateral sides.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:96 |
|---|---|
| Enthalten in: |
Journal of medical virology - 96(2024), 4 vom: 22. Apr., Seite e29579 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gandikota, Chaitanya [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 05.04.2024 Date Revised 05.04.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1002/jmv.29579 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370623525 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370623525 | ||
| 003 | DE-627 | ||
| 005 | 20240405234348.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240405s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/jmv.29579 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1366.xml |
| 035 | |a (DE-627)NLM370623525 | ||
| 035 | |a (NLM)38572923 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gandikota, Chaitanya |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The use of human iPSC-derived alveolar organoids to explore SARS-CoV-2 variant infections and host responses |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 05.04.2024 | ||
| 500 | |a Date Revised 05.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 Wiley Periodicals LLC. | ||
| 520 | |a Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) primarily targets the respiratory system. Physiologically relevant human lung models are indispensable to investigate virus-induced host response and disease pathogenesis. In this study, we generated human induced pluripotent stem cell (iPSC)-derived alveolar organoids (AOs) using an established protocol that recapitulates the sequential steps of in vivo lung development. AOs express alveolar epithelial type II cell protein markers including pro-surfactant protein C and ATP binding cassette subfamily A member 3. Compared to primary human alveolar type II cells, AOs expressed higher mRNA levels of SARS-CoV-2 entry factors, angiotensin-converting enzyme 2 (ACE2), asialoglycoprotein receptor 1 (ASGR1) and basigin (CD147). Considering the localization of ACE2 on the apical side in AOs, we used three AO models, apical-in, sheared and apical-out for SARS-CoV-2 infection. All three models of AOs were robustly infected with the SARS-CoV-2 irrespective of ACE2 accessibility. Antibody blocking experiment revealed that ASGR1 was the main receptor for SARS-CoV2 entry from the basolateral in apical-in AOs. AOs supported the replication of SARS-CoV-2 variants WA1, Alpha, Beta, Delta, and Zeta and Omicron to a variable degree with WA1 being the highest and Omicron being the least. Transcriptomic profiling of infected AOs revealed the induction of inflammatory and interferon-related pathways with NF-κB signaling being the predominant host response. In summary, iPSC-derived AOs can serve as excellent human lung models to investigate infection of SARS-CoV-2 variants and host responses from both apical and basolateral sides | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a SARS coronavirus | |
| 650 | 4 | |a immune responses | |
| 650 | 4 | |a innate immunity | |
| 650 | 4 | |a pathogenesis | |
| 650 | 4 | |a virus classification | |
| 650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 650 | 7 | |a ASGR1 protein, human |2 NLM | |
| 650 | 7 | |a Asialoglycoprotein Receptor |2 NLM | |
| 700 | 1 | |a Vaddadi, Kishore |e verfasserin |4 aut | |
| 700 | 1 | |a Sivasami, Pulavendran |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Chaoqun |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Yurong |e verfasserin |4 aut | |
| 700 | 1 | |a Pushparaj, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Xufang |e verfasserin |4 aut | |
| 700 | 1 | |a Channappanava, Rudragouda |e verfasserin |4 aut | |
| 700 | 1 | |a Metcalf, Jordan P |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Lin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of medical virology |d 1980 |g 96(2024), 4 vom: 22. Apr., Seite e29579 |w (DE-627)NLM000285676 |x 1096-9071 |7 nnns |
| 773 | 1 | 8 | |g volume:96 |g year:2024 |g number:4 |g day:22 |g month:04 |g pages:e29579 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/jmv.29579 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 96 |j 2024 |e 4 |b 22 |c 04 |h e29579 | ||