title: A systematic view on influenza induced host shutoff.
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.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Bercovich-Kinori
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Julie
authors.initials: J
authors.lastname: Tai
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Idit Anna
authors.initials: IA
authors.lastname: Gelbart
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Shitrit
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Ben-Moshe
authors.affiliation: Central Virology Laboratory, Chaim Sheba Medical Center, Ministry of Health, Rehovot, Israel.|Department of Epidemiology and Preventive Medicine, Tel-Aviv University, Tel-Aviv, Israel.|School of Public Health, Tel-Aviv University, Tel-Aviv, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Drori
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shalev
authors.identifier: 0000-0003-0685-2522
authors.initials: S
authors.lastname: Itzkovitz
authors.affiliation: Central Virology Laboratory, Chaim Sheba Medical Center, Ministry of Health, Rehovot, Israel.|Department of Epidemiology and Preventive Medicine, Tel-Aviv University, Tel-Aviv, Israel.|School of Public Health, Tel-Aviv University, Tel-Aviv, Israel.|Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Mandelboim
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Noam
authors.identifier: 0000-0003-3583-5932
authors.initials: N
authors.lastname: Stern-Ginossar
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000502:physiology / Q000821:virology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D010085:Oxidative Phosphorylation; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000096:biosynthesis*
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins
keywords: computational biology; host shutoff; human; infectious disease; microbiology; systems biology; translation; virus infection