Diverse effects of coronavirus-defective viral genomes on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication
Abstract Background The mechanism by which coronavirus-defective viral genomes (DVGs) affect coronavirus and host cells during infection remains unclear. A variety of DVGs with different RNA structures can be synthesized from coronavirus-infected cells, and these DVGs can also encode proteins. Conse...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | Virology Journal |
| Online Access: | https://doi.org/10.1186/s12985-025-02654-5 |
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| author | Hsuan-Wei Hsu Li-Kang Chang Chun-Chun Yang Ching-Hung Lin Yu Teng Pei-Chi Hsu Cheng-Yao Yang Hung-Yi Wu |
| author_facet | Hsuan-Wei Hsu Li-Kang Chang Chun-Chun Yang Ching-Hung Lin Yu Teng Pei-Chi Hsu Cheng-Yao Yang Hung-Yi Wu |
| author_sort | Hsuan-Wei Hsu |
| collection | DOAJ |
| description | Abstract Background The mechanism by which coronavirus-defective viral genomes (DVGs) affect coronavirus and host cells during infection remains unclear. A variety of DVGs with different RNA structures can be synthesized from coronavirus-infected cells, and these DVGs can also encode proteins. Consequently, in the present study, we first dissected the effects of individual DVGs on the synthesis of IFNβ and ISG15 mRNAs at the RNA, protein and combined levels, and then examined whether different coronavirus-DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions. Methods To dissect the effects of individual DVGs on the synthesis of IFNβ and ISG15 mRNAs at the RNA, protein and combined levels, DVG 2.2 and DVG 5.1, which were previously identified in coronavirus-infected cells, and their mutants were constructed followed by transfection. Western blot and RT‒qPCR were used to detect the synthesis of protein and to quantify the synthesis of IFNβ and ISG15 mRNAs, respectively. To examined whether different coronavirus-DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions, different naturally occurring DVGs were selected and constructed followed by transfection after or before coronavirus infection and by RT‒qPCR and hemagglutination assay. Results These results suggested that (i) coronavirus-DVGs at the RNA, protein and combined levels have different effects on the synthesis of IFNβ and ISG15 mRNAs, (ii) coronavirus-DVGs can inhibit coronavirus replication at least partly through interferon signaling and (iii) different DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions. Conclusions Coronavirus replication can be regulated by diverse coronavirus-derived DVGs at least partly through innate immunity. Such regulation may contribute to the pathogenesis of coronavirus. The DVG populations in coronavirus-infected cells with the ability to inhibit coronavirus replication are expected to be potential resources for the identification of antivirals at the level of RNA, protein or in combination, and the methods used in the current study can be used as a platform for this purpose. |
| format | Article |
| id | doaj-art-185920d64ced4006bccd5f403a9f7998 |
| institution | OA Journals |
| issn | 1743-422X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj-art-185920d64ced4006bccd5f403a9f79982025-08-20T02:13:07ZengBMCVirology Journal1743-422X2025-02-0122111710.1186/s12985-025-02654-5Diverse effects of coronavirus-defective viral genomes on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replicationHsuan-Wei Hsu0Li-Kang Chang1Chun-Chun Yang2Ching-Hung Lin3Yu Teng4Pei-Chi Hsu5Cheng-Yao Yang6Hung-Yi Wu7Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing UniversityGraduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing UniversityGraduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing UniversityDepartment of Veterinary Medicine, National Pingtung University of Science and TechnologyGraduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing UniversityGraduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing UniversityGraduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing UniversityGraduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing UniversityAbstract Background The mechanism by which coronavirus-defective viral genomes (DVGs) affect coronavirus and host cells during infection remains unclear. A variety of DVGs with different RNA structures can be synthesized from coronavirus-infected cells, and these DVGs can also encode proteins. Consequently, in the present study, we first dissected the effects of individual DVGs on the synthesis of IFNβ and ISG15 mRNAs at the RNA, protein and combined levels, and then examined whether different coronavirus-DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions. Methods To dissect the effects of individual DVGs on the synthesis of IFNβ and ISG15 mRNAs at the RNA, protein and combined levels, DVG 2.2 and DVG 5.1, which were previously identified in coronavirus-infected cells, and their mutants were constructed followed by transfection. Western blot and RT‒qPCR were used to detect the synthesis of protein and to quantify the synthesis of IFNβ and ISG15 mRNAs, respectively. To examined whether different coronavirus-DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions, different naturally occurring DVGs were selected and constructed followed by transfection after or before coronavirus infection and by RT‒qPCR and hemagglutination assay. Results These results suggested that (i) coronavirus-DVGs at the RNA, protein and combined levels have different effects on the synthesis of IFNβ and ISG15 mRNAs, (ii) coronavirus-DVGs can inhibit coronavirus replication at least partly through interferon signaling and (iii) different DVGs have different effects on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication both individually and collectively under different infection conditions. Conclusions Coronavirus replication can be regulated by diverse coronavirus-derived DVGs at least partly through innate immunity. Such regulation may contribute to the pathogenesis of coronavirus. The DVG populations in coronavirus-infected cells with the ability to inhibit coronavirus replication are expected to be potential resources for the identification of antivirals at the level of RNA, protein or in combination, and the methods used in the current study can be used as a platform for this purpose.https://doi.org/10.1186/s12985-025-02654-5 |
| spellingShingle | Hsuan-Wei Hsu Li-Kang Chang Chun-Chun Yang Ching-Hung Lin Yu Teng Pei-Chi Hsu Cheng-Yao Yang Hung-Yi Wu Diverse effects of coronavirus-defective viral genomes on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication Virology Journal |
| title | Diverse effects of coronavirus-defective viral genomes on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication |
| title_full | Diverse effects of coronavirus-defective viral genomes on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication |
| title_fullStr | Diverse effects of coronavirus-defective viral genomes on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication |
| title_full_unstemmed | Diverse effects of coronavirus-defective viral genomes on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication |
| title_short | Diverse effects of coronavirus-defective viral genomes on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication |
| title_sort | diverse effects of coronavirus defective viral genomes on the synthesis of ifnβ and isg15 mrnas and coronavirus replication |
| url | https://doi.org/10.1186/s12985-025-02654-5 |
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