Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids
ABSTRACTPatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-in...
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Format: | Article |
Language: | English |
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Taylor & Francis Group
2023-12-01
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Series: | Emerging Microbes and Infections |
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Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2023.2211685 |
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author | Min Jung Kim Sumi Kim Heeyeon Kim Dayeon Gil Hyeong-Jun Han Rajesh K. Thimmulappa Jang-Hoon Choi Jung-Hyun Kim |
author_facet | Min Jung Kim Sumi Kim Heeyeon Kim Dayeon Gil Hyeong-Jun Han Rajesh K. Thimmulappa Jang-Hoon Choi Jung-Hyun Kim |
author_sort | Min Jung Kim |
collection | DOAJ |
description | ABSTRACTPatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-induced alveolar type II organoids (hiAT2). hiAT2 organoids were susceptible to infection by both viruses and had features of severe lung damage. A single virus markedly enhanced the susceptibility to other virus infections. SARS-CoV-2 delta variants upregulated α-2-3-linked sialic acid, while FLUAV upregulated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Moreover, coinfection by SARS-CoV-2 and FLUAV caused hyperactivation of proinflammatory and immune-related signaling pathways and cellular damage compared to a respective single virus in hiAT2 organoids. This study provides insight into molecular mechanisms underlying enhanced infectivity and severity in patients with co-infection of SARS-CoV-2 and FLUAV, which may aid in the development of therapeutics for such co-infection cases. |
first_indexed | 2024-03-11T16:35:23Z |
format | Article |
id | doaj.art-9efe5bfd5a0b4471ad1622fd8508c0ec |
institution | Directory Open Access Journal |
issn | 2222-1751 |
language | English |
last_indexed | 2024-03-11T16:35:23Z |
publishDate | 2023-12-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Emerging Microbes and Infections |
spelling | doaj.art-9efe5bfd5a0b4471ad1622fd8508c0ec2023-10-23T17:36:54ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512023-12-0112110.1080/22221751.2023.2211685Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoidsMin Jung Kim0Sumi Kim1Heeyeon Kim2Dayeon Gil3Hyeong-Jun Han4Rajesh K. Thimmulappa5Jang-Hoon Choi6Jung-Hyun Kim7Division of Intractable Diseases Research, Department of Chronic Diseases Convergence Research, Korea National Institute of Health, Cheongju, KoreaDivision of Acute Viral Disease, Center for Emerging Virus Research, National Institute of Infectious Diseases, Korea National Institute of Health, Cheongju, KoreaDivision of Acute Viral Disease, Center for Emerging Virus Research, National Institute of Infectious Diseases, Korea National Institute of Health, Cheongju, KoreaDivision of Intractable Diseases Research, Department of Chronic Diseases Convergence Research, Korea National Institute of Health, Cheongju, KoreaDivision of Intractable Diseases Research, Department of Chronic Diseases Convergence Research, Korea National Institute of Health, Cheongju, KoreaDepartment of Biochemistry, Center of Excellence in Molecular Biology and Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru, IndiaDivision of Acute Viral Disease, Center for Emerging Virus Research, National Institute of Infectious Diseases, Korea National Institute of Health, Cheongju, KoreaDivision of Intractable Diseases Research, Department of Chronic Diseases Convergence Research, Korea National Institute of Health, Cheongju, KoreaABSTRACTPatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-induced alveolar type II organoids (hiAT2). hiAT2 organoids were susceptible to infection by both viruses and had features of severe lung damage. A single virus markedly enhanced the susceptibility to other virus infections. SARS-CoV-2 delta variants upregulated α-2-3-linked sialic acid, while FLUAV upregulated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Moreover, coinfection by SARS-CoV-2 and FLUAV caused hyperactivation of proinflammatory and immune-related signaling pathways and cellular damage compared to a respective single virus in hiAT2 organoids. This study provides insight into molecular mechanisms underlying enhanced infectivity and severity in patients with co-infection of SARS-CoV-2 and FLUAV, which may aid in the development of therapeutics for such co-infection cases.https://www.tandfonline.com/doi/10.1080/22221751.2023.2211685WordSARS-CoV-2Influenza A virusviral entry receptorDelta variantOmicron variant |
spellingShingle | Min Jung Kim Sumi Kim Heeyeon Kim Dayeon Gil Hyeong-Jun Han Rajesh K. Thimmulappa Jang-Hoon Choi Jung-Hyun Kim Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids Emerging Microbes and Infections Word SARS-CoV-2 Influenza A virus viral entry receptor Delta variant Omicron variant |
title | Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids |
title_full | Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids |
title_fullStr | Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids |
title_full_unstemmed | Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids |
title_short | Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids |
title_sort | reciprocal enhancement of sars cov 2 and influenza virus replication in human pluripotent stem cell derived lung organoids |
topic | Word SARS-CoV-2 Influenza A virus viral entry receptor Delta variant Omicron variant |
url | https://www.tandfonline.com/doi/10.1080/22221751.2023.2211685 |
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