Influenza virus infection induces widespread alterations of host cell splicing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA646750 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12243954_1.fastq.gz | Fastqsanger.gz | |||
| SRR12243954_2.fastq.gz | Fastqsanger.gz | |||
| SRR12243955_1.fastq.gz | Fastqsanger.gz | |||
| SRR12243955_2.fastq.gz | Fastqsanger.gz | |||
| SRR12243956_1.fastq.gz | Fastqsanger.gz |
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Project description:Influenza A viruses (IAV) use diverse mechanisms to interfere with cellular gene expression and thus limit the antiviral responses and/or promote viral replication. Although many RNAseq studies have documented IAV-induced changes in host mRNA abundance, few were designed to allow an accurate quantification of changes in host mRNA splicing. Here we show that IAV infection of human lung cells induces widespread alterations of cellular splicing, with an overall increase in exon inclusion and decrease in intron retention. Over half of the mRNAs that show differential splicing undergo no significant changes in abundance or in their 3’ end termination site, suggesting that IAV can directly manipulate cellular splicing independently of other transcriptional changes. Cross-analysis of the alternative splicing profiles of IAV-infected and RED-depleted cells demonstrates a partial phenocopying of the RED-knock down phenotype in infected cells, suggesting that hijacking of the RED factor by IAVs to promote splicing of their own mRNAs could account for a minor subset of splicing changes in infected cells. All our results can be expored through a Shiny user friendly interface (http://virhostnet.prabi.fr:3838/shinyapps/flu-splicing).
2020-08-31 | GSE154596 | GEO
Project description:Influenza A viruses (IAVs) use diverse mechanisms to interfere with cellular gene expression. Although many RNA-seq studies have documented IAV-induced changes in host mRNA abundance, few were designed to allow an accurate quantification of changes in host mRNA splicing. Here, we show that IAV infection of human lung cells induces widespread alterations of cellular splicing, with an overall increase in exon inclusion and decrease in intron retention. Over half of the mRNAs that show differential splicing undergo no significant changes in abundance or in their 3' end termination site, suggesting that IAVs can specifically manipulate cellular splicing. Among a randomly selected subset of 21 IAV-sensitive alternative splicing events, most are specific to IAV infection as they are not observed upon infection with VSV, induction of interferon expression or induction of an osmotic stress. Finally, the analysis of splicing changes in RED-depleted cells reveals a limited but significant overlap with the splicing changes in IAV-infected cells. This observation suggests that hijacking of RED by IAVs to promote splicing of the abundant viral NS1 mRNAs could partially divert RED from its target mRNAs. All our RNA-seq datasets and analyses are made accessible for browsing through a user-friendly Shiny interface (http://virhostnet.prabi.fr:3838/shinyapps/flu-splicing or https://github.com/cbenoitp/flu-splicing).
| S-EPMC7680258 | biostudies-literature
Project description:Competition and interplay between host and viral gene expression programs is a critical determinant of infection susceptibility and a potential target for anti-viral therapies. Viral infection is well documented to induce the expression of numerous host genes that are part of the innate immune response. Here we show that infection of human lung epithelial cells with Influenza A virus (IAV) also induces a broad program of alternative splicing of host genes. While these splicing-regulated genes are not enriched for known regulators of viral infection, we find that many of these genes do modulate the infection and/or replication of IAV in an siRNA screen. Moreover, inhibition of the IAV-induced splicing pattern in several genes tested also reduces viral infection. We further show that approximately a quarter of the IAV-induced splicing events are regulated by hnRNP K, a host protein we have previously implicated in the nuclear speckle-dependent splicing of the IAV M transcript. Notably, hnRNP K abundance at nuclear speckles is increased upon IAV infection. We propose that this change in subnuclear localization may alter the accessibility of hnRNP K for host transcripts, thereby leading to a program of host splicing changes that promote IAV replication.
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Project description:Viral-Induced Alternative Splicing of Host Genes Promotes Influenza Replication
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Project description:A century ago, influenza A virus (IAV) infection caused the 1918 flu pandemic and killed an estimated 20-40 million people. Pandemic IAV outbreaks occur when strains from animal reservoirs acquire the ability to infect and spread among humans. The molecular details of this species barrier are incompletely understood. We combined metabolic pulse labeling and quantitative shotgun proteomics to globally monitor protein synthesis upon infection of human cells with a human- and a bird-adapted IAV strain. While production of host proteins was remarkably similar, we observed striking differences in the kinetics of viral protein synthesis over the course of infection. Most importantly, the matrix protein M1 was inefficiently produced by the bird-adapted strain at later stages. We show that impaired production of M1 from bird-adapted strains is caused by increased splicing of the M segment RNA to alternative isoforms. Experiments with reporter constructs and recombinant influenza viruses revealed that strain-specific M segment splicing is controlled by the 3’ splice site and functionally important for permissive infection. Independent in silico and biochemical evidence shows that avian-adapted M segments have evolved different conserved RNA structure features than human-adapted sequences. Thus, our data identifies M segment RNA splicing as a viral determinant of host range.
2019-11-11 | PXD015475 | Pride
Project description:A century ago, influenza A virus (IAV) infection caused the 1918 flu pandemic and killed an estimated 20-40 million people. Pandemic IAV outbreaks occur when strains from animal reservoirs acquire the ability to infect and spread among humans. The molecular details of this species barrier are incompletely understood. We combined metabolic pulse labeling and quantitative shotgun proteomics to globally monitor protein synthesis upon infection of human cells with a human- and a bird-adapted IAV strain. While production of host proteins was remarkably similar, we observed striking differences in the kinetics of viral protein synthesis over the course of infection. Most importantly, the matrix protein M1 was inefficiently produced by the bird-adapted strain at later stages. We show that impaired production of M1 from bird-adapted strains is caused by increased splicing of the M segment RNA to alternative isoforms. Experiments with reporter constructs and recombinant influenza viruses revealed that strain-specific M segment splicing is controlled by the 3’ splice site and functionally important for permissive infection. Independent in silico and biochemical evidence shows that avian-adapted M segments have evolved different conserved RNA structure features than human-adapted sequences. Thus, our data identifies M segment RNA splicing as a viral determinant of host range.
2019-11-11 | PXD015474 | Pride
Project description:Widespread regulated alternative splicing of single codons accelerates proteome evolution
| PRJNA143693 | ENA
Project description:This SuperSeries is composed of the following subset Series: GSE36461: MiRNA profiling during infection with H1N1 influenza A virus (A/Mexico/InDRE4487/H1N1/2009) GSE36462: MiRNA profiling during infection with H7N7 influenza A virus (A/Ck/Germany/R28/H7N7/2003) GSE36553: mRNA profiling during infection with H1N1 influenza A virus (A/Mexico/InDRE4487/H1N1/2009) Refer to individual Series
2012-04-09 | E-GEOD-36555 | biostudies-arrayexpress
Project description:Our study's objective was to determine circRNA expression alterations following in vivo influenza virus infection. We challenged C57BL/6 for 48 hours with IAV-PR8. Lung samples were obtained, RNA-Seq was utilized, and the circRNAs transcriptome data was compared to the control.
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