NAR Genom Bioinform . Influenza virus infection induces widespread alterations of host cell splicing

[tetano]

NAR Genom Bioinform


. 2020 Nov 21;2(4):lqaa095.
doi: 10.1093/nargab/lqaa095. eCollection 2020 Dec.
Influenza virus infection induces widespread alterations of host cell splicing


Usama Ashraf ¹ , Clara Benoit-Pilven ² , Vincent Navratil ³ , C?cile Ligneau ¹ , Guillaume Fournier ¹ , Sandie Munier ¹ , Odile Sismeiro ⁴ , Jean-Yves Copp?e ⁴ , Vincent Lacroix ⁵ , Nadia Naffakh ¹



Affiliations

• PMID: 33575639
• PMCID: PMC7680258
• DOI: 10.1093/nargab/lqaa095

Abstract

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).