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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Main Authors: Yu-Jing Zeng, Min-Kung Hsu, Chiao-An Tsai, Chun-Yen Chu, Hsing-Chieh Wu, Hsian-Yu Wang
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/9/6/601
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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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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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