Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells.
Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (β-CoVs) that have caused significant morbidity and mortality worldwide. Therefore, a better understanding of host responses to β-CoVs would provide insights into the pathogenesis of these viruses...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0317921 |
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| author | Vivian Y Tat Aleksandra K Drelich Pinghan Huang Kamil Khanipov Jason C Hsu Steven G Widen Chien-Te Kent Tseng George Golovko |
| author_facet | Vivian Y Tat Aleksandra K Drelich Pinghan Huang Kamil Khanipov Jason C Hsu Steven G Widen Chien-Te Kent Tseng George Golovko |
| author_sort | Vivian Y Tat |
| collection | DOAJ |
| description | Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (β-CoVs) that have caused significant morbidity and mortality worldwide. Therefore, a better understanding of host responses to β-CoVs would provide insights into the pathogenesis of these viruses to identify potential targets for medical countermeasures. In this study, our objective is to use a systems biology approach to explore the magnitude and scope of innate immune responses triggered by SARS-CoV-1 and -2 infection over time in pathologically relevant human lung epithelial cells (Calu-3/2B4 cells). Total RNA extracted at 12, 24, and 48 hours after β-CoVs or mock infection of Calu-3/2B4 cells were subjected to RNA sequencing and functional enrichment analysis to select genes whose expressions were significantly modulated post-infection. The results demonstrate that SARS-CoV-1 and -2 stimulate similar yet distinct innate antiviral signaling pathways in pathologically relevant human lung epithelial cells. Furthermore, we found that many genes related to the viral life cycle, interferons, and interferon-stimulated genes (ISGs) were upregulated at multiple time points. Based on their profound modulation upon infection by SARS-CoV-1, SARS-CoV-2, and Omicron BA.1, four ISGs, i.e., bone marrow stromal cell antigen 2 (BST2), Z-DNA Binding Protein 1 (ZBP1), C-X-C Motif Chemokine Ligand 11 (CXCL11), and Interferon Induced Transmembrane Protein 1 (IFITM1), were identified as potential drug targets against β-CoVs. Our findings suggest that these genes affect both pathogens directly and indirectly through the innate immune response, making them potential targets for host-directed antivirals. Altogether, our results demonstrate that SARS-CoV-1 and SARS-CoV-2 infection induce differential effects on host innate immune responses. |
| format | Article |
| id | doaj-art-ef4e80beecce444d99275424a83e5605 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-ef4e80beecce444d99275424a83e56052025-02-05T05:31:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031792110.1371/journal.pone.0317921Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells.Vivian Y TatAleksandra K DrelichPinghan HuangKamil KhanipovJason C HsuSteven G WidenChien-Te Kent TsengGeorge GolovkoSevere acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (β-CoVs) that have caused significant morbidity and mortality worldwide. Therefore, a better understanding of host responses to β-CoVs would provide insights into the pathogenesis of these viruses to identify potential targets for medical countermeasures. In this study, our objective is to use a systems biology approach to explore the magnitude and scope of innate immune responses triggered by SARS-CoV-1 and -2 infection over time in pathologically relevant human lung epithelial cells (Calu-3/2B4 cells). Total RNA extracted at 12, 24, and 48 hours after β-CoVs or mock infection of Calu-3/2B4 cells were subjected to RNA sequencing and functional enrichment analysis to select genes whose expressions were significantly modulated post-infection. The results demonstrate that SARS-CoV-1 and -2 stimulate similar yet distinct innate antiviral signaling pathways in pathologically relevant human lung epithelial cells. Furthermore, we found that many genes related to the viral life cycle, interferons, and interferon-stimulated genes (ISGs) were upregulated at multiple time points. Based on their profound modulation upon infection by SARS-CoV-1, SARS-CoV-2, and Omicron BA.1, four ISGs, i.e., bone marrow stromal cell antigen 2 (BST2), Z-DNA Binding Protein 1 (ZBP1), C-X-C Motif Chemokine Ligand 11 (CXCL11), and Interferon Induced Transmembrane Protein 1 (IFITM1), were identified as potential drug targets against β-CoVs. Our findings suggest that these genes affect both pathogens directly and indirectly through the innate immune response, making them potential targets for host-directed antivirals. Altogether, our results demonstrate that SARS-CoV-1 and SARS-CoV-2 infection induce differential effects on host innate immune responses.https://doi.org/10.1371/journal.pone.0317921 |
| spellingShingle | Vivian Y Tat Aleksandra K Drelich Pinghan Huang Kamil Khanipov Jason C Hsu Steven G Widen Chien-Te Kent Tseng George Golovko Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells. PLoS ONE |
| title | Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells. |
| title_full | Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells. |
| title_fullStr | Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells. |
| title_full_unstemmed | Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells. |
| title_short | Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells. |
| title_sort | characterizing temporal and global host innate immune responses against sars cov 1 and 2 infection in pathologically relevant human lung epithelial cells |
| url | https://doi.org/10.1371/journal.pone.0317921 |
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