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...

Full description

Saved in:
Bibliographic Details
Main Authors: Marisa Mendes, Alistair B Russell
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-12-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010125&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850075001597722624
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