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The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions


Viruses are fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt it for their own benefit. However, fundamental questions such as: what is the effect that infection has on the spectrum of host mRNAs that are being translated, and whether, and to what extent, a virus possesses mechanisms to commandeer the translation machinery are still hard to address. Here we show that by simultaneously examining the changes in transcription and translation along Human cytomegalovirus (HCMV) infection, we can uncover extensive transcriptional regulation, but also diverse and dynamic translational control. We were also able to show that, at late time points in infection, translation of viral mRNAs is higher than that of cellular mRNAs. Lastly, we take advantage of our measurements of translation (protein synthesis rate) and integrate these with mass spectrometry measurements (protein abundance). This integration allowed us to unbiasedly reveal dozens of cellular proteins that are being degraded during HCMV infection. Since targeted degradation indicates a strong biological importance, this approach should be applicable for discovering central host functions during viral infection. Our work provides a framework for studying the contribution of transcription, translation and degradation during infection with any virus.


Vyšlo v časopise: The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005288
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005288

Souhrn

Viruses are fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt it for their own benefit. However, fundamental questions such as: what is the effect that infection has on the spectrum of host mRNAs that are being translated, and whether, and to what extent, a virus possesses mechanisms to commandeer the translation machinery are still hard to address. Here we show that by simultaneously examining the changes in transcription and translation along Human cytomegalovirus (HCMV) infection, we can uncover extensive transcriptional regulation, but also diverse and dynamic translational control. We were also able to show that, at late time points in infection, translation of viral mRNAs is higher than that of cellular mRNAs. Lastly, we take advantage of our measurements of translation (protein synthesis rate) and integrate these with mass spectrometry measurements (protein abundance). This integration allowed us to unbiasedly reveal dozens of cellular proteins that are being degraded during HCMV infection. Since targeted degradation indicates a strong biological importance, this approach should be applicable for discovering central host functions during viral infection. Our work provides a framework for studying the contribution of transcription, translation and degradation during infection with any virus.


Zdroje

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