A systematic view on influenza induced host shutoff

Adi Bercovich-Kinori, Julie Tai, Idit Anna Gelbart, Alina Shitrit, Shani Ben-Moshe, Yaron Drori, Shalev Itzkovitz, Michal Mandelboim, Noam Stern-Ginossar

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Host shutoff is a common strategy used by viruses to repress cellular mRNA translation and concomitantly allow the efficient translation of viral mRNAs. Here we use RNA-sequencing and ribosome profiling to explore the mechanisms that are being utilized by the Influenza A virus (IAV) to induce host shutoff. We show that viral transcripts are not preferentially translated and instead the decline in cellular protein synthesis is mediated by viral takeover on the mRNA pool. Our measurements also uncover strong variability in the levels of cellular transcripts reduction, revealing that short transcripts are less affected by IAV. Interestingly, these mRNAs that are refractory to IAV infection are enriched in cell maintenance processes such as oxidative phosphorylation. Furthermore, we show that the continuous oxidative phosphorylation activity is important for viral propagation. Our results advance our understanding of IAV-induced shutoff, and suggest a mechanism that facilitates the translation of genes with important housekeeping functions.

    Original languageEnglish
    Article numbere18311
    JournaleLife
    Volume5
    Issue numberAUGUST
    DOIs
    StatePublished - 15 Aug 2016

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