flu-splicing

The software tool "flu-splicing" is designed to investigate and quantify changes in host mRNA splicing induced by Influenza A virus (IAV) infections. This tool emerged from studies that recognized the need for a focused analysis of how IAV infection alters cellular splicing beyond the changes in mRNA abundance or 3' end termination site alterations. The key findings and features of this tool include:

1. Induction of Splicing Alterations by IAV: The tool documents that IAV infection leads to significant changes in cellular splicing patterns within human lung cells. An increased exon inclusion and decreased intron retention indicate that IAV can specifically manipulate splicing mechanisms.

2. Specificity to IAV Infection: Analysis of a subset of IAV-sensitive alternative splicing events revealed that most of these changes are specific to IAV infection. This specificity is evidenced by the lack of observed changes upon infection with Vesicular Stomatitis Virus (VSV), upon induction of interferon expression, or under osmotic stress conditions.

3. Minimal Changes in mRNA Abundance: Over half of the mRNAs exhibiting differential splicing showed no significant changes in abundance or their 3' end termination sites. This finding underscores the targeted impact of IAV on the splicing process without altering mRNA levels.

4. Interplay with RED Protein: The analysis highlighted a connection between IAV infection and manipulating the cellular protein RED. IAVs appear to hijack RED to promote splicing its viral NS1 mRNAs, which could divert RED from its normal cellular targets. The study found a significant overlap in splicing changes between IAV-infected cells and cells with depleted RED levels, suggesting that IAV's manipulation of RED partially contributes to the observed splicing alterations.

5. Accessibility and User Interface: This study's datasets and analyses are accessible through a user-friendly Shiny interface.