Respiratory syncytial virus (RSV) enhances translation of virus-resembling AU-rich host transcripts
Abstract Background 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 tr...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
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| Series: | Virology Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12985-025-02838-z |
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| Summary: | Abstract Background 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. Methods 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. Results 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). Conclusions These findings revealed that RSV changes the translational landscape by enhancing translation of virus-resembling AU-rich host transcripts rather than inhibiting host translation. |
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| ISSN: | 1743-422X |