The influenza A virus (IAV) genome consists of eight negative-sense viral RNA (vRNA) segments that are selectively assembled into progeny virus particles through RNA-RNA interactions. To explore putative intersegmental RNA-RNA relationships, we quantified similarity between phylogenetic trees comprising each vRNA segment from seasonal human IAV. Intersegmental tree similarity differed between subtype and lineage. While intersegmental relationships were largely conserved over time in H3N2 viruses, they diverged in H1N1 strains isolated before and after the 2009 pandemic. Surprisingly, intersegmental relationships were not driven solely by protein sequence, suggesting that IAV evolution could also be driven by RNA-RNA interactions. Finally, we used confocal microscopy to determine that colocalization of highly coevolved vRNA segments is enriched over other assembly intermediates at the nuclear periphery during productive viral infection. This study illustrates how putative RNA interactions underlying selective assembly of IAV can be interrogated with phylogenetics.
All data generated or analysed during this study are included in the manuscript and supporting files. Scripts have been deposited to GitHub as described in the manuscript. Summary tables have been provided for Figures 2-7 and figure supplements.
Influenza Research Database: An integrated bioinformatics resource for influenza virus researchInfluenza Research Database, doi: 10.1093/nar/gkw857.
- Jennifer E Jones
- Jennifer E Jones
- Seema S Lakdawala
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Imroze Khan, Ashoka University, India
- Received: January 14, 2021
- Accepted: August 23, 2021
- Accepted Manuscript published: August 27, 2021 (version 1)
© 2021, Jones et al.
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