Parallel evolution between genomic segments of seasonal human influenza viruses reveals RNA-RNA relationships
- University of Pittsburgh, United States
Abstract
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.
Data availability
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.
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Influenza Research Database: An integrated bioinformatics resource for influenza virus researchInfluenza Research Database, doi: 10.1093/nar/gkw857.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (T32 AI049820)
- Jennifer E Jones
Center for Evolutionary Biology and Medicine, University of Pittsburgh
- Jennifer E Jones
National Institute of Allergy and Infectious Diseases (R01 AI139063)
- Seema S Lakdawala
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Jones et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Parallel evolution between genomic segments of seasonal human influenza viruses reveals RNA-RNA relationships
eLife 10:e66525.
https://doi.org/10.7554/eLife.66525
Further reading
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- Evolutionary Biology
- Epidemiology and Global Health
- Microbiology and Infectious Disease
- Genetics and Genomics
eLife is pleased to present a Special Issue to highlight recent advances in the growing and increasingly interdisciplinary field of evolutionary medicine.
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- Evolutionary Biology
The majority of highly polymorphic genes are related to immune functions and with over 100 alleles within a population, genes of the major histocompatibility complex (MHC) are the most polymorphic loci in vertebrates. How such extraordinary polymorphism arose and is maintained is controversial. One possibility is heterozygote advantage (HA), which can in principle maintain any number of alleles, but biologically explicit models based on this mechanism have so far failed to reliably predict the coexistence of significantly more than ten alleles. We here present an eco-evolutionary model showing that evolution can result in the emergence and maintenance of more than 100 alleles under HA if the following two assumptions are fulfilled: first, pathogens are lethal in the absence of an appropriate immune defence; second, the effect of pathogens depends on host condition, with hosts in poorer condition being affected more strongly. Thus, our results show that HA can be a more potent force in explaining the extraordinary polymorphism found at MHC loci than currently recognized.
