A statistical framework for quantifying the nuclear export rate of influenza viral mRNAs

Abstract

<p>Influenza A virus acutely transcribes viral mRNAs from the eight segmented viral genome when it infects. The kinetics of viral transcription, nuclear export of viral transcripts, and their potential variation between the eight segments are poorly characterised. Here we introduce a statistical framework for estimating the nuclear export rate of each segment from a snapshot of mRNA <em>in situ</em> localisation at a single time point, exploiting the cell-to-cell variation observed by an imaging-based <em>in situ</em> transcriptome assay. A mathematical modelling indicated that the relationship between the nuclear ratio and the total count of mRNAs in single cells is dictated by a proxy for the nuclear export rate. Using this model, we showed that the two influenza viral antigens hemagglutinin and neuraminidase were the slowest segments in the nuclear export, suggesting that influenza A virus uses the nuclear retention of viral transcripts to delay the expression of antigenic molecules. Our framework presented in this study can be widely used for investigating the nuclear retention of nascent transcripts produced in a transcription burst.<br></p>