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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2025-07-01
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| Series: | Virology Journal |
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| Online Access: | https://doi.org/10.1186/s12985-025-02838-z |
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| author | Kyra Kerkhofs Nicholas R. Guydosh Mark A. Bayfield |
| author_facet | Kyra Kerkhofs Nicholas R. Guydosh Mark A. Bayfield |
| author_sort | Kyra Kerkhofs |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e179db629dac4a00bd38059bec598d63 |
| institution | DOAJ |
| issn | 1743-422X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj-art-e179db629dac4a00bd38059bec598d632025-08-20T03:04:10ZengBMCVirology Journal1743-422X2025-07-0122111910.1186/s12985-025-02838-zRespiratory syncytial virus (RSV) enhances translation of virus-resembling AU-rich host transcriptsKyra Kerkhofs0Nicholas R. Guydosh1Mark A. Bayfield2Department of Biology, Faculty of Science, York UniversitySection On mRNA Regulation and Translation, Laboratory of Biochemistry & Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthDepartment of Biology, Faculty of Science, York UniversityAbstract 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.https://doi.org/10.1186/s12985-025-02838-zRSVVSVTranslation efficiencyPolysome profilingHigh-throughput sequencingAU-rich transcripts |
| spellingShingle | Kyra Kerkhofs Nicholas R. Guydosh Mark A. Bayfield Respiratory syncytial virus (RSV) enhances translation of virus-resembling AU-rich host transcripts Virology Journal RSV VSV Translation efficiency Polysome profiling High-throughput sequencing AU-rich transcripts |
| title | Respiratory syncytial virus (RSV) enhances translation of virus-resembling AU-rich host transcripts |
| title_full | Respiratory syncytial virus (RSV) enhances translation of virus-resembling AU-rich host transcripts |
| title_fullStr | Respiratory syncytial virus (RSV) enhances translation of virus-resembling AU-rich host transcripts |
| title_full_unstemmed | Respiratory syncytial virus (RSV) enhances translation of virus-resembling AU-rich host transcripts |
| title_short | Respiratory syncytial virus (RSV) enhances translation of virus-resembling AU-rich host transcripts |
| title_sort | respiratory syncytial virus rsv enhances translation of virus resembling au rich host transcripts |
| topic | RSV VSV Translation efficiency Polysome profiling High-throughput sequencing AU-rich transcripts |
| url | https://doi.org/10.1186/s12985-025-02838-z |
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