A systematic view on Influenza induced host shut-off
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 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.
Data availability
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A systematic view on Influenza induced host shut-offPublicly available at the NCBI Gene Expression Omnibus (accession no. GSE82232).
Article and author information
Author details
Funding
Human Frontier Science Program
- Noam Stern-Ginossar
Israel Science Foundation
- Noam Stern-Ginossar
Israeli Centers for Research Excellence
- Noam Stern-Ginossar
European Research Council
- Noam Stern-Ginossar
Marie Curie integration grant
- Noam Stern-Ginossar
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Nahum Sonenberg, McGill University, Canada
Version history
- Received: May 30, 2016
- Accepted: August 14, 2016
- Accepted Manuscript published: August 15, 2016 (version 1)
- Version of Record published: September 19, 2016 (version 2)
Copyright
© 2016, Bercovich-Kinori et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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