Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness
Abstract Viral genomes not only code the protein content, but also include silent, overlapping codes which are important to the regulation of the viral life cycle and affect its evolution. Due to the high density of these codes, their non-modular nature and the complex intracellular processes they e...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-89918-6 |
| _version_ | 1818840728960237568 |
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| author | Lia Baron Shimshi Atar Hadas Zur Modi Roopin Eli Goz Tamir Tuller |
| author_facet | Lia Baron Shimshi Atar Hadas Zur Modi Roopin Eli Goz Tamir Tuller |
| author_sort | Lia Baron |
| collection | DOAJ |
| description | Abstract Viral genomes not only code the protein content, but also include silent, overlapping codes which are important to the regulation of the viral life cycle and affect its evolution. Due to the high density of these codes, their non-modular nature and the complex intracellular processes they encode, the ability of current approaches to decipher them is very limited. We describe the first computational-experimental pipeline for studying the effects of viral silent and non-silent information on its fitness. The pipeline was implemented to study the Porcine Circovirus type 2 (PCV2), the shortest known eukaryotic virus, and includes the following steps: (1) Based on the analyses of 2100 variants of PCV, suspected silent codes were inferred. (2) Five hundred variants of the PCV2 were designed to include various ‘smart’ silent mutations. (3) Using state of the art synthetic biology approaches, the genomes of these five hundred variants were generated. (4) Competition experiments between the variants were performed in Porcine kidney-15 (PK15) cell-lines. (5) The variant titers were analyzed based on novel next-generation sequencing (NGS) experiments. (6) The features related to the titer of the variants were inferred and their analyses enabled detection of various novel silent functional sequence and structural motifs. Furthermore, we demonstrate that 50 of the silent variants exhibit higher fitness than the wildtype in the analyzed conditions. |
| first_indexed | 2024-12-19T04:14:48Z |
| format | Article |
| id | doaj.art-e9a8f059b8c9470f84d002f5d313aabe |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:14:48Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e9a8f059b8c9470f84d002f5d313aabe2022-12-21T20:36:20ZengNature PortfolioScientific Reports2045-23222021-05-0111111710.1038/s41598-021-89918-6Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitnessLia Baron0Shimshi Atar1Hadas Zur2Modi Roopin3Eli Goz4Tamir Tuller5Department of Biomedical Engineering, Tel-Aviv UniversityDepartment of Biomedical Engineering, Tel-Aviv UniversityDepartment of Biomedical Engineering, Tel-Aviv UniversityDepartment of Biomedical Engineering, Tel-Aviv UniversityDepartment of Biomedical Engineering, Tel-Aviv UniversityDepartment of Biomedical Engineering, Tel-Aviv UniversityAbstract Viral genomes not only code the protein content, but also include silent, overlapping codes which are important to the regulation of the viral life cycle and affect its evolution. Due to the high density of these codes, their non-modular nature and the complex intracellular processes they encode, the ability of current approaches to decipher them is very limited. We describe the first computational-experimental pipeline for studying the effects of viral silent and non-silent information on its fitness. The pipeline was implemented to study the Porcine Circovirus type 2 (PCV2), the shortest known eukaryotic virus, and includes the following steps: (1) Based on the analyses of 2100 variants of PCV, suspected silent codes were inferred. (2) Five hundred variants of the PCV2 were designed to include various ‘smart’ silent mutations. (3) Using state of the art synthetic biology approaches, the genomes of these five hundred variants were generated. (4) Competition experiments between the variants were performed in Porcine kidney-15 (PK15) cell-lines. (5) The variant titers were analyzed based on novel next-generation sequencing (NGS) experiments. (6) The features related to the titer of the variants were inferred and their analyses enabled detection of various novel silent functional sequence and structural motifs. Furthermore, we demonstrate that 50 of the silent variants exhibit higher fitness than the wildtype in the analyzed conditions.https://doi.org/10.1038/s41598-021-89918-6 |
| spellingShingle | Lia Baron Shimshi Atar Hadas Zur Modi Roopin Eli Goz Tamir Tuller Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness Scientific Reports |
| title | Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness |
| title_full | Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness |
| title_fullStr | Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness |
| title_full_unstemmed | Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness |
| title_short | Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness |
| title_sort | computational based design and tracking of synthetic variants of porcine circovirus reveal relations between silent genomic information and viral fitness |
| url | https://doi.org/10.1038/s41598-021-89918-6 |
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