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Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains
BACKGROUND: Pseudorabies virus (PRV) of the family Herpesviridae is the causative agent of Aujeszky’s disease. Attenuation of PRV by serial passaging in vitro is a well-established method; however, the dynamic variations occurring on viral genome during this process have not been characterized. METH...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310976/ https://www.ncbi.nlm.nih.gov/pubmed/30594230 http://dx.doi.org/10.1186/s12985-018-1102-8 |
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author | Ye, Chao Wu, Jiqiang Tong, Wu Shan, Tongling Cheng, Xuefei Xu, Jingjing Liang, Chao Zheng, Hao Li, Guoxin Tong, Guangzhi |
author_facet | Ye, Chao Wu, Jiqiang Tong, Wu Shan, Tongling Cheng, Xuefei Xu, Jingjing Liang, Chao Zheng, Hao Li, Guoxin Tong, Guangzhi |
author_sort | Ye, Chao |
collection | PubMed |
description | BACKGROUND: Pseudorabies virus (PRV) of the family Herpesviridae is the causative agent of Aujeszky’s disease. Attenuation of PRV by serial passaging in vitro is a well-established method; however, the dynamic variations occurring on viral genome during this process have not been characterized. METHODS: Genome sequencing and comparative genomic analyses of a virulent pseudorabies virus and a series of its plaque-purified strains via serial passaging in vitro were performed, and the properties in vitro and in vivo of which were further characterized. RESULTS: Compared to the parental virus, replication in vitro was enhanced in the highly passaged F50, F91, and F120. In contrast, lethality in mice decreased gradually with passage number. Genome sequencing of F50, F91, and F120 showed deletion of a large fragment containing gE, which is likely related to their attenuation. In addition, single nucleotide variations were identified in many genes of F50, F91, and F120. In-frame and frameshift indels were also detected in specific genes of passaged strains. Particularly frameshift mutations were observed in highly passaged strains, resulting in a truncated but overexpressed pUL46. CONCLUSION: During attenuation of PRV by serial passaging in Vero cells, dynamic variation patterns including a large deletion, single nucleotide variations, small in-frame indels, and also frameshifts mutations successively emerged, contributing to evolution of the viral population and enabling the gradual attenuation of the virus. These data provide clues to better understand PRV attenuation during passaging. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1102-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6310976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63109762019-01-07 Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains Ye, Chao Wu, Jiqiang Tong, Wu Shan, Tongling Cheng, Xuefei Xu, Jingjing Liang, Chao Zheng, Hao Li, Guoxin Tong, Guangzhi Virol J Short Report BACKGROUND: Pseudorabies virus (PRV) of the family Herpesviridae is the causative agent of Aujeszky’s disease. Attenuation of PRV by serial passaging in vitro is a well-established method; however, the dynamic variations occurring on viral genome during this process have not been characterized. METHODS: Genome sequencing and comparative genomic analyses of a virulent pseudorabies virus and a series of its plaque-purified strains via serial passaging in vitro were performed, and the properties in vitro and in vivo of which were further characterized. RESULTS: Compared to the parental virus, replication in vitro was enhanced in the highly passaged F50, F91, and F120. In contrast, lethality in mice decreased gradually with passage number. Genome sequencing of F50, F91, and F120 showed deletion of a large fragment containing gE, which is likely related to their attenuation. In addition, single nucleotide variations were identified in many genes of F50, F91, and F120. In-frame and frameshift indels were also detected in specific genes of passaged strains. Particularly frameshift mutations were observed in highly passaged strains, resulting in a truncated but overexpressed pUL46. CONCLUSION: During attenuation of PRV by serial passaging in Vero cells, dynamic variation patterns including a large deletion, single nucleotide variations, small in-frame indels, and also frameshifts mutations successively emerged, contributing to evolution of the viral population and enabling the gradual attenuation of the virus. These data provide clues to better understand PRV attenuation during passaging. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1102-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-29 /pmc/articles/PMC6310976/ /pubmed/30594230 http://dx.doi.org/10.1186/s12985-018-1102-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Short Report Ye, Chao Wu, Jiqiang Tong, Wu Shan, Tongling Cheng, Xuefei Xu, Jingjing Liang, Chao Zheng, Hao Li, Guoxin Tong, Guangzhi Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains |
title | Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains |
title_full | Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains |
title_fullStr | Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains |
title_full_unstemmed | Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains |
title_short | Comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains |
title_sort | comparative genomic analyses of a virulent pseudorabies virus and a series of its in vitro passaged strains |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310976/ https://www.ncbi.nlm.nih.gov/pubmed/30594230 http://dx.doi.org/10.1186/s12985-018-1102-8 |
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