Differentially expressed ncRNAs as key regulators in infection of human bronchial epithelial cells by the SARS-CoV-2 Delta variant
SARS-CoV-2 infection initiates complex interactions at mucosal barriers. In primary human bronchial epithelial cells, we investigated changes in the small RNA transcriptome induced by Delta variant infection. Thereby, we uncovered differential expression of a specific set of microRNAs (miRNAs), PIWI...
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| Language: | English |
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Elsevier
2025-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253125001131 |
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| author | Glory Ranches Hubert Hackl Viktoria Zaderer Melanie Ploner Wilfried Posch Doris Wilflingseder Kai Kummer Alexander Hüttenhofer |
| author_facet | Glory Ranches Hubert Hackl Viktoria Zaderer Melanie Ploner Wilfried Posch Doris Wilflingseder Kai Kummer Alexander Hüttenhofer |
| author_sort | Glory Ranches |
| collection | DOAJ |
| description | SARS-CoV-2 infection initiates complex interactions at mucosal barriers. In primary human bronchial epithelial cells, we investigated changes in the small RNA transcriptome induced by Delta variant infection. Thereby, we uncovered differential expression of a specific set of microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), vault RNAs, Y RNAs, and long intergenic non-coding RNAs (lincRNAs), which inhibit apoptosis while promoting cell proliferation and viral infection. Conversely, differential expression of 7SL, U2, and RPPH1 RNAs, as well as miR-155-5p and miR-27a-5p, was found to be involved in antiviral signaling. In addition, expression of the protein-coding genes CXCL10, IFIT1, NCOA7, IFIT2, SIX3, and RPSA was increased during infection. Interestingly, the ribosomal protein RPSA has recently been reported to also serve as a viral surface receptor promoting pro-inflammatory cytokine signaling. By investigating these differentially expressed genes also after Omicron BA.2 variant infection, we observed a significantly lower expression of the protein-coding genes CXCL10, IFIT2, and ZC3HAV1. In contrast, expression changes for the majority of non-coding RNAs (ncRNAs) were similar between Delta and Omicron variants with the exception of miR-155-5p and 5′-tRFGlu(TTC), emphasizing their potential as biomarkers for disease severity. Our findings thus highlight distinct molecular responses in SARS-CoV-2-infected cells, revealing specific genes and ncRNAs involved in viral replication, immune response, and apoptosis. |
| format | Article |
| id | doaj-art-a13701cc13b745b3a0ffc0cac4b7e70b |
| institution | DOAJ |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-a13701cc13b745b3a0ffc0cac4b7e70b2025-08-20T03:21:51ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-06-0136210255910.1016/j.omtn.2025.102559Differentially expressed ncRNAs as key regulators in infection of human bronchial epithelial cells by the SARS-CoV-2 Delta variantGlory Ranches0Hubert Hackl1Viktoria Zaderer2Melanie Ploner3Wilfried Posch4Doris Wilflingseder5Kai Kummer6Alexander Hüttenhofer7Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria; Division of Genomics and RNomics, Biocenter, Medical University Innsbruck, Innsbruck, AustriaInstitute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, AustriaDivision of Genomics and RNomics, Biocenter, Medical University Innsbruck, Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, University of Veterinary Medicine, Vienna, Austria; Corresponding author: Doris Wilflingseder, Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.Institute of Physiology, Medical University of Innsbruck, Innsbruck, Austria; Corresponding author: Kai Kummer, Institute of Physiology, Medical University of Innsbruck, Innsbruck, Austria.Division of Genomics and RNomics, Biocenter, Medical University Innsbruck, Innsbruck, Austria; Corresponding author: Alexander Huettenhofer, Division of Genomics and RNomics, Biocenter, Medical University Innsbruck, Innsbruck, Austria.SARS-CoV-2 infection initiates complex interactions at mucosal barriers. In primary human bronchial epithelial cells, we investigated changes in the small RNA transcriptome induced by Delta variant infection. Thereby, we uncovered differential expression of a specific set of microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), vault RNAs, Y RNAs, and long intergenic non-coding RNAs (lincRNAs), which inhibit apoptosis while promoting cell proliferation and viral infection. Conversely, differential expression of 7SL, U2, and RPPH1 RNAs, as well as miR-155-5p and miR-27a-5p, was found to be involved in antiviral signaling. In addition, expression of the protein-coding genes CXCL10, IFIT1, NCOA7, IFIT2, SIX3, and RPSA was increased during infection. Interestingly, the ribosomal protein RPSA has recently been reported to also serve as a viral surface receptor promoting pro-inflammatory cytokine signaling. By investigating these differentially expressed genes also after Omicron BA.2 variant infection, we observed a significantly lower expression of the protein-coding genes CXCL10, IFIT2, and ZC3HAV1. In contrast, expression changes for the majority of non-coding RNAs (ncRNAs) were similar between Delta and Omicron variants with the exception of miR-155-5p and 5′-tRFGlu(TTC), emphasizing their potential as biomarkers for disease severity. Our findings thus highlight distinct molecular responses in SARS-CoV-2-infected cells, revealing specific genes and ncRNAs involved in viral replication, immune response, and apoptosis.http://www.sciencedirect.com/science/article/pii/S2162253125001131MT: Non-coding RNAsSARS-CoV-2non-coding RNAstranscriptomic profilevirus variantspathways |
| spellingShingle | Glory Ranches Hubert Hackl Viktoria Zaderer Melanie Ploner Wilfried Posch Doris Wilflingseder Kai Kummer Alexander Hüttenhofer Differentially expressed ncRNAs as key regulators in infection of human bronchial epithelial cells by the SARS-CoV-2 Delta variant Molecular Therapy: Nucleic Acids MT: Non-coding RNAs SARS-CoV-2 non-coding RNAs transcriptomic profile virus variants pathways |
| title | Differentially expressed ncRNAs as key regulators in infection of human bronchial epithelial cells by the SARS-CoV-2 Delta variant |
| title_full | Differentially expressed ncRNAs as key regulators in infection of human bronchial epithelial cells by the SARS-CoV-2 Delta variant |
| title_fullStr | Differentially expressed ncRNAs as key regulators in infection of human bronchial epithelial cells by the SARS-CoV-2 Delta variant |
| title_full_unstemmed | Differentially expressed ncRNAs as key regulators in infection of human bronchial epithelial cells by the SARS-CoV-2 Delta variant |
| title_short | Differentially expressed ncRNAs as key regulators in infection of human bronchial epithelial cells by the SARS-CoV-2 Delta variant |
| title_sort | differentially expressed ncrnas as key regulators in infection of human bronchial epithelial cells by the sars cov 2 delta variant |
| topic | MT: Non-coding RNAs SARS-CoV-2 non-coding RNAs transcriptomic profile virus variants pathways |
| url | http://www.sciencedirect.com/science/article/pii/S2162253125001131 |
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