Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways
© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC..
Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFNγ treatment does not significantly modulate the expression of SARS-CoV-2 entry-related factors and induces a similar level of pro-inflammatory response in human lung tissues when compared with IFNβ treatment. Mechanistically, we show that overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), which is most profoundly induced by IFNγ, substantially restricts the replication of ancestral SARS-CoV-2 and the Alpha and Delta variants. Meanwhile, loss-of-function study reveals that IDO1 knockdown restores SARS-CoV-2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l-tryptophan, a substrate of IDO1, partially rescues the IFNγ-mediated inhibitory effect on SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type-II IFN potently inhibits SARS-CoV-2 replication through IDO1-mediated antiviral response.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:96 |
|---|---|
| Enthalten in: |
Journal of medical virology - 96(2024), 2 vom: 19. Feb., Seite e29472 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yang, Dong [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
9008-11-1 |
|---|
| Anmerkungen: |
Date Completed 21.02.2024 Date Revised 21.02.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1002/jmv.29472 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368632601 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368632601 | ||
| 003 | DE-627 | ||
| 005 | 20240222092012.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240220s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/jmv.29472 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1301.xml |
| 035 | |a (DE-627)NLM368632601 | ||
| 035 | |a (NLM)38373201 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Yang, Dong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways |
| 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 21.02.2024 | ||
| 500 | |a Date Revised 21.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. | ||
| 520 | |a Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFNγ treatment does not significantly modulate the expression of SARS-CoV-2 entry-related factors and induces a similar level of pro-inflammatory response in human lung tissues when compared with IFNβ treatment. Mechanistically, we show that overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), which is most profoundly induced by IFNγ, substantially restricts the replication of ancestral SARS-CoV-2 and the Alpha and Delta variants. Meanwhile, loss-of-function study reveals that IDO1 knockdown restores SARS-CoV-2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l-tryptophan, a substrate of IDO1, partially rescues the IFNγ-mediated inhibitory effect on SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type-II IFN potently inhibits SARS-CoV-2 replication through IDO1-mediated antiviral response | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a IDO1 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a ex vivo human lung tissues | |
| 650 | 4 | |a indoleamine 2,3-dioxygenase | |
| 650 | 4 | |a interferon | |
| 650 | 4 | |a type-II IFN | |
| 650 | 7 | |a Indoleamine-Pyrrole 2,3,-Dioxygenase |2 NLM | |
| 650 | 7 | |a Interferons |2 NLM | |
| 650 | 7 | |a 9008-11-1 |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 700 | 1 | |a Chan, Jasper Fuk-Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Yoon, Chaemin |e verfasserin |4 aut | |
| 700 | 1 | |a Luk, Tsz-Yat |e verfasserin |4 aut | |
| 700 | 1 | |a Shuai, Huiping |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Yuxin |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xiner |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Bingjie |e verfasserin |4 aut | |
| 700 | 1 | |a Chai, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Terrence Tsz-Tai |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yuanchen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Tianrenzheng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Huan |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Jialu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yixin |e verfasserin |4 aut | |
| 700 | 1 | |a Sit, Ko-Yung |e verfasserin |4 aut | |
| 700 | 1 | |a Au, Wing-Kuk |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Anna Jinxia |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Shuofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Bao-Zhong |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yao-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Hin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of medical virology |d 1990 |g 96(2024), 2 vom: 19. Feb., Seite e29472 |w (DE-627)NLM000285676 |x 1096-9071 |7 nnns |
| 773 | 1 | 8 | |g volume:96 |g year:2024 |g number:2 |g day:19 |g month:02 |g pages:e29472 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/jmv.29472 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 96 |j 2024 |e 2 |b 19 |c 02 |h e29472 | ||