A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes.
Defective viral genomes of the copy-back type (cbDVGs) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus (RSV) both in vitro and in vivo. However, the mechanism governing cbDVG generation remains unknown, thereby limiting our ability to man...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-04-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1007707 |
| _version_ | 1797660737095598080 |
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| author | Yan Sun Eun Ji Kim Sébastien A Felt Louis J Taylor Divyansh Agarwal Gregory R Grant Carolina B López |
| author_facet | Yan Sun Eun Ji Kim Sébastien A Felt Louis J Taylor Divyansh Agarwal Gregory R Grant Carolina B López |
| author_sort | Yan Sun |
| collection | DOAJ |
| description | Defective viral genomes of the copy-back type (cbDVGs) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus (RSV) both in vitro and in vivo. However, the mechanism governing cbDVG generation remains unknown, thereby limiting our ability to manipulate cbDVG content in order to modulate the host response to infection. Here we report a specific genomic signal that mediates the generation of a subset of RSV cbDVG species. Using a customized bioinformatics tool, we identified regions in the RSV genome frequently used to generate cbDVGs during infection. We then created a minigenome system to validate the function of one of these sequences and to determine if specific nucleotides were essential for cbDVG generation at that position. Further, we created a recombinant virus unable to produce a subset of cbDVGs due to mutations introduced in this sequence. The identified sequence was also found as a site for cbDVG generation during natural RSV infections, and common cbDVGs originated at this sequence were found among samples from various infected patients. These data demonstrate that sequences encoded in the viral genome determine the location of cbDVG formation and, therefore, the generation of cbDVGs is not a stochastic process. These findings open the possibility of genetically manipulating cbDVG formation to modulate infection outcome. |
| first_indexed | 2024-03-11T18:35:18Z |
| format | Article |
| id | doaj.art-c9ed71e811864fa081c42fb6cc344dd6 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-11T18:35:18Z |
| publishDate | 2019-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-c9ed71e811864fa081c42fb6cc344dd62023-10-13T05:31:14ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-04-01154e100770710.1371/journal.ppat.1007707A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes.Yan SunEun Ji KimSébastien A FeltLouis J TaylorDivyansh AgarwalGregory R GrantCarolina B LópezDefective viral genomes of the copy-back type (cbDVGs) are the primary initiators of the antiviral immune response during infection with respiratory syncytial virus (RSV) both in vitro and in vivo. However, the mechanism governing cbDVG generation remains unknown, thereby limiting our ability to manipulate cbDVG content in order to modulate the host response to infection. Here we report a specific genomic signal that mediates the generation of a subset of RSV cbDVG species. Using a customized bioinformatics tool, we identified regions in the RSV genome frequently used to generate cbDVGs during infection. We then created a minigenome system to validate the function of one of these sequences and to determine if specific nucleotides were essential for cbDVG generation at that position. Further, we created a recombinant virus unable to produce a subset of cbDVGs due to mutations introduced in this sequence. The identified sequence was also found as a site for cbDVG generation during natural RSV infections, and common cbDVGs originated at this sequence were found among samples from various infected patients. These data demonstrate that sequences encoded in the viral genome determine the location of cbDVG formation and, therefore, the generation of cbDVGs is not a stochastic process. These findings open the possibility of genetically manipulating cbDVG formation to modulate infection outcome.https://doi.org/10.1371/journal.ppat.1007707 |
| spellingShingle | Yan Sun Eun Ji Kim Sébastien A Felt Louis J Taylor Divyansh Agarwal Gregory R Grant Carolina B López A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes. PLoS Pathogens |
| title | A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes. |
| title_full | A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes. |
| title_fullStr | A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes. |
| title_full_unstemmed | A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes. |
| title_short | A specific sequence in the genome of respiratory syncytial virus regulates the generation of copy-back defective viral genomes. |
| title_sort | specific sequence in the genome of respiratory syncytial virus regulates the generation of copy back defective viral genomes |
| url | https://doi.org/10.1371/journal.ppat.1007707 |
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