Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes.
Found in a diverse set of viral populations, defective interfering particles are parasitic variants that are unable to replicate on their own yet rise to relatively high frequencies. Their presence is associated with a loss of population fitness, both through the depletion of key cellular resources...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010125&type=printable |
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| _version_ | 1850075001597722624 |
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| author | Marisa Mendes Alistair B Russell |
| author_facet | Marisa Mendes Alistair B Russell |
| author_sort | Marisa Mendes |
| collection | DOAJ |
| description | Found in a diverse set of viral populations, defective interfering particles are parasitic variants that are unable to replicate on their own yet rise to relatively high frequencies. Their presence is associated with a loss of population fitness, both through the depletion of key cellular resources and the stimulation of innate immunity. For influenza A virus, these particles contain large internal deletions in the genomic segments which encode components of the heterotrimeric polymerase. Using a library-based approach, we comprehensively profile the growth and replication of defective influenza species, demonstrating that they possess an advantage during genome replication, and that exclusion during population expansion reshapes population composition in a manner consistent with their final, observed, distribution in natural populations. We find that an innate immune response is not linked to the size of a deletion; however, replication of defective segments can enhance their immunostimulatory properties. Overall, our results address several key questions in defective influenza A virus biology, and the methods we have developed to answer those questions may be broadly applied to other defective viruses. |
| format | Article |
| id | doaj-art-81df3fb370bf4617a3df01358e7072b4 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-81df3fb370bf4617a3df01358e7072b42025-08-20T02:46:25ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-12-011712e101012510.1371/journal.ppat.1010125Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes.Marisa MendesAlistair B RussellFound in a diverse set of viral populations, defective interfering particles are parasitic variants that are unable to replicate on their own yet rise to relatively high frequencies. Their presence is associated with a loss of population fitness, both through the depletion of key cellular resources and the stimulation of innate immunity. For influenza A virus, these particles contain large internal deletions in the genomic segments which encode components of the heterotrimeric polymerase. Using a library-based approach, we comprehensively profile the growth and replication of defective influenza species, demonstrating that they possess an advantage during genome replication, and that exclusion during population expansion reshapes population composition in a manner consistent with their final, observed, distribution in natural populations. We find that an innate immune response is not linked to the size of a deletion; however, replication of defective segments can enhance their immunostimulatory properties. Overall, our results address several key questions in defective influenza A virus biology, and the methods we have developed to answer those questions may be broadly applied to other defective viruses.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010125&type=printable |
| spellingShingle | Marisa Mendes Alistair B Russell Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes. PLoS Pathogens |
| title | Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes. |
| title_full | Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes. |
| title_fullStr | Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes. |
| title_full_unstemmed | Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes. |
| title_short | Library-based analysis reveals segment and length dependent characteristics of defective influenza genomes. |
| title_sort | library based analysis reveals segment and length dependent characteristics of defective influenza genomes |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010125&type=printable |
| work_keys_str_mv | AT marisamendes librarybasedanalysisrevealssegmentandlengthdependentcharacteristicsofdefectiveinfluenzagenomes AT alistairbrussell librarybasedanalysisrevealssegmentandlengthdependentcharacteristicsofdefectiveinfluenzagenomes |