# Respiratory syncytial virus (RSV) enhances translation of virus-resembling AU-rich host transcripts

## TL;DR

This study shows that RSV boosts the translation of AU-rich host mRNAs that resemble viral transcripts, altering the cell's translational landscape during infection.

## Contribution

The study reveals a novel mechanism by which RSV enhances translation of AU-rich host transcripts without globally inhibiting translation.

## Key findings

- RSV increases ribosome loading on mRNAs during infection, as shown by higher polysome fractions.
- Virus-resembling AU-rich host transcripts become more efficient at ribosome recruitment during RSV infection.
- Similar trends were observed in VSV-infected cells, suggesting a broader viral strategy.

## Abstract

Viruses strongly rely on the host’s translational machinery to produce viral proteins required for replication. However, it is unknown how viruses that do not globally inhibit cap-dependent translation compete with abundant host transcripts for ribosomes. Viral infection often triggers eukaryotic initiator factor 2α (eIF2α) phosphorylation, leading to global 5’-cap-dependent translation inhibition. Respiratory syncytial virus (RSV) encodes mRNAs mimicking 5’-cap structures of host mRNAs and thus inhibition of cap-dependent translation initiation would likely also reduce viral translation.

RSV-infected HEp-2 and A549 cells were analyzed to determine translation levels using western blotting, indirect immunofluorescent staining and polysome profiling. Transcriptome-wide translation efficiencies of virus-infected cells were compared against mock-infected cells using high-throughput sequencing of poly(A)-tail enriched total mRNA and transcripts associated with heavy polysomes.

We confirmed that RSV limits widespread translation initiation inhibition and unexpectedly found that the fraction of ribosomes within polysomes increases during infection, indicating higher ribosome loading on mRNAs during infection. High-throughput sequencing revealed that virus-resembling, AU-rich host transcripts become more efficient at ribosome recruitment. Using a previously published dataset, we observe similar trends in another negative-sense single-stranded RNA virus, vesicular stomatitis virus (VSV).

These findings revealed that RSV changes the translational landscape by enhancing translation of virus-resembling AU-rich host transcripts rather than inhibiting host translation.

The online version contains supplementary material available at 10.1186/s12985-025-02838-z.