A Senescence-Like Cellular Response Inhibits Bovine Ephemeral Fever Virus Proliferation
During industrial-scale production of viruses for vaccine manufacturing, anti-viral response of host cells can dampen maximal viral antigen yield. In addition to interferon responses, many other cellular responses, such as the AMPK signaling pathway or senescence-like response may inhibit or slow do...
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MDPI AG
2021-06-01
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author | Yu-Jing Zeng Min-Kung Hsu Chiao-An Tsai Chun-Yen Chu Hsing-Chieh Wu Hsian-Yu Wang |
author_facet | Yu-Jing Zeng Min-Kung Hsu Chiao-An Tsai Chun-Yen Chu Hsing-Chieh Wu Hsian-Yu Wang |
author_sort | Yu-Jing Zeng |
collection | DOAJ |
description | During industrial-scale production of viruses for vaccine manufacturing, anti-viral response of host cells can dampen maximal viral antigen yield. In addition to interferon responses, many other cellular responses, such as the AMPK signaling pathway or senescence-like response may inhibit or slow down virus amplification in the cell culture system. In this study, we first performed a Gene Set Enrichment Analysis of the whole-genome mRNA transcriptome and found a senescence-like cellular response in BHK-21 cells when infected with bovine ephemeral fever virus (BEFV). To demonstrate that this senescence-like state may reduce virus growth, BHK-21 subclones showing varying degrees of a senescence-like state were infected with BEFV. The results showed that the BHK-21 subclones showing high senescence staining could inhibit BEFV replication while low senescence-staining subclones are permissive to virus replication. Using a different approach, a senescence-like state was induced in BHK-21 using a small molecule, camptothecin (CPT), and BEFV susceptibility were examined. The results showed that CPT-treated BHK-21 is more resistant to virus infection. Overall, these results indicate that a senescence-like response may be at play in BHK-21 upon virus infection. Furthermore, cell clone selection and modulating treatments using small molecules may be tools in countering anti-viral responses. |
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id | doaj.art-1657a3aff8774b9994e4fcb504ffe347 |
institution | Directory Open Access Journal |
issn | 2076-393X |
language | English |
last_indexed | 2024-03-10T10:41:39Z |
publishDate | 2021-06-01 |
publisher | MDPI AG |
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series | Vaccines |
spelling | doaj.art-1657a3aff8774b9994e4fcb504ffe3472023-11-21T22:51:40ZengMDPI AGVaccines2076-393X2021-06-019660110.3390/vaccines9060601A Senescence-Like Cellular Response Inhibits Bovine Ephemeral Fever Virus ProliferationYu-Jing Zeng0Min-Kung Hsu1Chiao-An Tsai2Chun-Yen Chu3Hsing-Chieh Wu4Hsian-Yu Wang5International Program in Animal Vaccine Technology, International College, National Pingtung University of Science and Technology, Pingtung 91201, TaiwanResearch Center for Tumor Medical Science, China Medical University, Taichung 40402, TaiwanGraduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91201, TaiwanInternational Program in Animal Vaccine Technology, International College, National Pingtung University of Science and Technology, Pingtung 91201, TaiwanInternational Program in Animal Vaccine Technology, International College, National Pingtung University of Science and Technology, Pingtung 91201, TaiwanInternational Program in Animal Vaccine Technology, International College, National Pingtung University of Science and Technology, Pingtung 91201, TaiwanDuring industrial-scale production of viruses for vaccine manufacturing, anti-viral response of host cells can dampen maximal viral antigen yield. In addition to interferon responses, many other cellular responses, such as the AMPK signaling pathway or senescence-like response may inhibit or slow down virus amplification in the cell culture system. In this study, we first performed a Gene Set Enrichment Analysis of the whole-genome mRNA transcriptome and found a senescence-like cellular response in BHK-21 cells when infected with bovine ephemeral fever virus (BEFV). To demonstrate that this senescence-like state may reduce virus growth, BHK-21 subclones showing varying degrees of a senescence-like state were infected with BEFV. The results showed that the BHK-21 subclones showing high senescence staining could inhibit BEFV replication while low senescence-staining subclones are permissive to virus replication. Using a different approach, a senescence-like state was induced in BHK-21 using a small molecule, camptothecin (CPT), and BEFV susceptibility were examined. The results showed that CPT-treated BHK-21 is more resistant to virus infection. Overall, these results indicate that a senescence-like response may be at play in BHK-21 upon virus infection. Furthermore, cell clone selection and modulating treatments using small molecules may be tools in countering anti-viral responses.https://www.mdpi.com/2076-393X/9/6/601anti-viral responsesenescence-like responseviral vaccine productionBEFV<i>Rhabdoviridae</i>GSEA |
spellingShingle | Yu-Jing Zeng Min-Kung Hsu Chiao-An Tsai Chun-Yen Chu Hsing-Chieh Wu Hsian-Yu Wang A Senescence-Like Cellular Response Inhibits Bovine Ephemeral Fever Virus Proliferation Vaccines anti-viral response senescence-like response viral vaccine production BEFV <i>Rhabdoviridae</i> GSEA |
title | A Senescence-Like Cellular Response Inhibits Bovine Ephemeral Fever Virus Proliferation |
title_full | A Senescence-Like Cellular Response Inhibits Bovine Ephemeral Fever Virus Proliferation |
title_fullStr | A Senescence-Like Cellular Response Inhibits Bovine Ephemeral Fever Virus Proliferation |
title_full_unstemmed | A Senescence-Like Cellular Response Inhibits Bovine Ephemeral Fever Virus Proliferation |
title_short | A Senescence-Like Cellular Response Inhibits Bovine Ephemeral Fever Virus Proliferation |
title_sort | senescence like cellular response inhibits bovine ephemeral fever virus proliferation |
topic | anti-viral response senescence-like response viral vaccine production BEFV <i>Rhabdoviridae</i> GSEA |
url | https://www.mdpi.com/2076-393X/9/6/601 |
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