Mapping of Influenza Virus RNA-RNA Interactions Reveals a Flexible Network

Sage, Valerie Le; Kanarek, Jack P.; Snyder, Dan; Cooper, Vaughn S.; Lakdawala, Seema S.; Lee, Nara

doi:10.1016/j.celrep.2020.107823

Cited by 59 publications

(92 citation statements)

References 29 publications

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“…We previously demonstrated that binding of vRNA segments by the NP protein is nonuniform and non-random (Le Sage et al, 2018;Lee et al, 2017), supporting the model that intersegmental RNA interactions facilitate selective assembly. Biochemical approaches to define bona fide intersegmental RNA-RNA interactions demonstrated that the interaction network is highly flexible and varies between H1N1 and H3N2 viruses (Dadonaite et al, 2019;Le Sage et al, 2020). These observations are consistent with our conclusion that RNA interactions constrain parallel evolution between vRNA segments in a manner sensitive to the genetic context studied.…”

Section: Discussionsupporting

confidence: 88%

“…Selective assembly of all eight genomic segments is fundamental to the production of fully infectious virus particles. We and others have used a variety of biochemical approaches to investigate the mechanisms that promote selective assembly (Dadonaite et al, 2019;Le Sage et al, 2020). We previously demonstrated that binding of vRNA segments by the NP protein is nonuniform and non-random (Le Sage et al, 2018;Lee et al, 2017), supporting the model that intersegmental RNA interactions facilitate selective assembly.…”

Section: Discussionmentioning

confidence: 81%

“…Such methodologies could be further employed to investigate epistasis arising from RNA-RNA interactions. Mounting evidence from our group and others suggests that direct intermolecular interactions between vRNA segments coordinate selective assembly (Dadonaite et al, 2019;Le Sage et al, 2020). Genomic assembly contributes to heterogeneity in progeny viruses and could determine the fitness of reassortant strains after coinfection (Brooke, 2017;Lowen, 2017).…”

Section: Introductionmentioning

confidence: 85%

“…Recent studies have identified a highly plastic and redundant network of interactions between vRNA segments in influenza virions produced during productive infection, many of which may be transient (Dadonaite et al, 2019;Le Sage et al, 2020). Based on these observations, it is plausible that vRNA relationships defined by parallel evolution change over time.…”

Section: Parallel Evolution Is Largely Conserved Over Time Within H3nmentioning

confidence: 99%

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Parallel evolution between genomic segments of seasonal human influenza viruses reveals RNA-RNA relationships

Jones

Sage

Padovani

et al. 2021

Preprint

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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 identify relationships between vRNA segments, we examined parallel evolution between vRNA segments of seasonal human IAV, finding that evolutionary relationships between vRNA segments differ between subtypes and antigenically-shifted strains. Intersegmental relationships were distinct between H3N2 and H1N1 viruses, but largely conserved over time in H3N2 viruses. However, parallel evolution of vRNA segments diverged between H1N1 strains isolated before and after the 2009 pandemic. Surprisingly, intersegmental relationships were not driven solely by protein sequence, which is potentially indicative of RNA-RNA driven coevolution. Colocalization of highly coevolved vRNA segments was enriched over other pairs at the nuclear periphery during a productive viral infection. This study illustrates how phylogenetics can be applied to interrogate putative RNA interactions underlying selective assembly of IAV.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 85%

Section: Parallel Evolution Is Largely Conserved Over Time Within H3nmentioning

confidence: 99%

See 2 more Smart Citations

Parallel evolution between genomic segments of seasonal human influenza viruses reveals RNA-RNA relationships

Jones

Sage

Padovani

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Contrary to other segmented RNA viruses like influenza virus and rotavirus, in which specific RNA-RNA interactions facilitate co-packaging of all the different viral genome segments 20,35,36 , a growing body of evidence supports the notion that bunyavirus genome packaging is rather flexible and non-selective 21 . Here, we show that less than 10% of RVFV and SBV progeny virions produced in mammalian cells contain the three genome segments, meaning that only a minor fraction of produced virus particles are infectious on their own (Fig.…”

Section: Discussionmentioning

confidence: 98%

Visualizing the RNP content of single bunyavirus virions reveals more efficient genome packaging in the arthropod host

Bermúdez-Méndez¹,

Katrukha²,

Spruit³

et al. 2020

Preprint

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Bunyaviruses have a genome that is divided over multiple segments. Genome segmentation complicates the generation of progeny virus, since each newly formed virus particle should preferably contain a full set of genome segments in order to disseminate efficiently within and between hosts. Here, we combine immunofluorescence and fluorescence in situ hybridization techniques to simultaneously visualize bunyavirus progeny virions and their genomic content at single-molecule resolution in the context of singly infected cells. Using Rift Valley fever virus and Schmallenberg virus as prototype tri-segmented bunyaviruses, we show that bunyavirus genome packaging is influenced by the intracellular viral genome content of individual cells, which results in greatly variable packaging efficiencies within a cell population. We further show that bunyavirus genome packaging is more efficient in insect cells compared to mammalian cells and provide new insights on the possibility that incomplete particles may contribute to bunyavirus spread as well.

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Local changes in viral RNA sequence drive global changes in influenza nucleoprotein binding

Sage

Kanarek

Lakdawala

et al. 2023

Journal of Medical Virology

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The genome of influenza A viruses (IAV) consists of eight negative-sense RNA segments that are coated by viral nucleoprotein (NP). Until recently, it was assumed that NP binds viral genomic RNA (vRNA) uniformly along the entire segment. However, genome-wide studies have revised the original model in that NP instead binds preferentially to certain regions of vRNA, while others are depleted for NP binding. Even strains with high sequence similarity exhibit distinct NP-binding profiles. Thus, it remains unknown how NP-binding specificity to vRNA is established. Here we introduced nucleotide changes to vRNA to examine whether

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Mapping of Influenza Virus RNA-RNA Interactions Reveals a Flexible Network

Cited by 59 publications

References 29 publications

Parallel evolution between genomic segments of seasonal human influenza viruses reveals RNA-RNA relationships

Parallel evolution between genomic segments of seasonal human influenza viruses reveals RNA-RNA relationships

Visualizing the RNP content of single bunyavirus virions reveals more efficient genome packaging in the arthropod host

Local changes in viral RNA sequence drive global changes in influenza nucleoprotein binding

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