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Effects of Coronavirus Persistence on the Genome Structure and Subsequent Gene Expression, Pathogenicity and Adaptation Capability

Coronaviruses are able to establish persistence. However, how coronaviruses react to persistence and whether the selected viruses have altered their characteristics remain unclear. In this study, we found that the persistent infection of bovine coronavirus (BCoV), which is in the same genus as SARS-...

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Autores principales: Lin, Ching-Hung, Yang, Cheng-Yao, Wang, Meilin, Ou, Shan-Chia, Lo, Chen-Yu, Tsai, Tsung-Lin, Wu, Hung-Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589090/
https://www.ncbi.nlm.nih.gov/pubmed/33086697
http://dx.doi.org/10.3390/cells9102322
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author Lin, Ching-Hung
Yang, Cheng-Yao
Wang, Meilin
Ou, Shan-Chia
Lo, Chen-Yu
Tsai, Tsung-Lin
Wu, Hung-Yi
author_facet Lin, Ching-Hung
Yang, Cheng-Yao
Wang, Meilin
Ou, Shan-Chia
Lo, Chen-Yu
Tsai, Tsung-Lin
Wu, Hung-Yi
author_sort Lin, Ching-Hung
collection PubMed
description Coronaviruses are able to establish persistence. However, how coronaviruses react to persistence and whether the selected viruses have altered their characteristics remain unclear. In this study, we found that the persistent infection of bovine coronavirus (BCoV), which is in the same genus as SARS-COV-2, led to alterations of genome structure, attenuation of gene expression, and the synthesis of subgenomic mRNA (sgmRNA) with a previously unidentified pattern. Subsequent analyses revealed that the altered genome structures were associated with the attenuation of gene expression. In addition, the genome structure at the 5′ terminus and the cellular environment during the persistence were responsible for the sgmRNA synthesis, solving the previously unanswered question regarding the selection of transcription regulatory sequence for synthesis of BCoV sgmRNA 12.7. Although the BCoV variants (BCoV-p95) selected under the persistence replicated efficiently in cells without persistent infection, its pathogenicity was still lower than that of wild-type (wt) BCoV. Furthermore, in comparison with wt BCoV, the variant BCoV-p95 was not able to efficiently adapt to the challenges of alternative environments, suggesting wt BCoV is genetically robust. We anticipate that the findings derived from this fundamental research can contribute to the disease control and treatments against coronavirus infection including SARS-CoV-2.
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spelling pubmed-75890902020-10-29 Effects of Coronavirus Persistence on the Genome Structure and Subsequent Gene Expression, Pathogenicity and Adaptation Capability Lin, Ching-Hung Yang, Cheng-Yao Wang, Meilin Ou, Shan-Chia Lo, Chen-Yu Tsai, Tsung-Lin Wu, Hung-Yi Cells Article Coronaviruses are able to establish persistence. However, how coronaviruses react to persistence and whether the selected viruses have altered their characteristics remain unclear. In this study, we found that the persistent infection of bovine coronavirus (BCoV), which is in the same genus as SARS-COV-2, led to alterations of genome structure, attenuation of gene expression, and the synthesis of subgenomic mRNA (sgmRNA) with a previously unidentified pattern. Subsequent analyses revealed that the altered genome structures were associated with the attenuation of gene expression. In addition, the genome structure at the 5′ terminus and the cellular environment during the persistence were responsible for the sgmRNA synthesis, solving the previously unanswered question regarding the selection of transcription regulatory sequence for synthesis of BCoV sgmRNA 12.7. Although the BCoV variants (BCoV-p95) selected under the persistence replicated efficiently in cells without persistent infection, its pathogenicity was still lower than that of wild-type (wt) BCoV. Furthermore, in comparison with wt BCoV, the variant BCoV-p95 was not able to efficiently adapt to the challenges of alternative environments, suggesting wt BCoV is genetically robust. We anticipate that the findings derived from this fundamental research can contribute to the disease control and treatments against coronavirus infection including SARS-CoV-2. MDPI 2020-10-19 /pmc/articles/PMC7589090/ /pubmed/33086697 http://dx.doi.org/10.3390/cells9102322 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Ching-Hung
Yang, Cheng-Yao
Wang, Meilin
Ou, Shan-Chia
Lo, Chen-Yu
Tsai, Tsung-Lin
Wu, Hung-Yi
Effects of Coronavirus Persistence on the Genome Structure and Subsequent Gene Expression, Pathogenicity and Adaptation Capability
title Effects of Coronavirus Persistence on the Genome Structure and Subsequent Gene Expression, Pathogenicity and Adaptation Capability
title_full Effects of Coronavirus Persistence on the Genome Structure and Subsequent Gene Expression, Pathogenicity and Adaptation Capability
title_fullStr Effects of Coronavirus Persistence on the Genome Structure and Subsequent Gene Expression, Pathogenicity and Adaptation Capability
title_full_unstemmed Effects of Coronavirus Persistence on the Genome Structure and Subsequent Gene Expression, Pathogenicity and Adaptation Capability
title_short Effects of Coronavirus Persistence on the Genome Structure and Subsequent Gene Expression, Pathogenicity and Adaptation Capability
title_sort effects of coronavirus persistence on the genome structure and subsequent gene expression, pathogenicity and adaptation capability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589090/
https://www.ncbi.nlm.nih.gov/pubmed/33086697
http://dx.doi.org/10.3390/cells9102322
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