Comprehensive characterisation of molecular host-pathogen interactions in influenza A virus-infected human macrophages
Comprehensive characterisation of molecular host-pathogen interactions in influenza A virus-infected human macrophages
Abstract Macrophages in the lung detect and respond to influenza A virus (IAV), determining the nature of the immune response. Using terminal depth 5’-RNA sequencing (CAGE) we quantify transcriptional activity of both host and pathogen over a 24-hour timecourse of IAV infection in primary human monocyte-derived macrophages (MDM). We use a systems approach to describe the transcriptional landscape of the host response to IAV contrasted with bacterial lipopolysaccharide treated MDMs, observing a failure of IAV-treated MDMs to induce feedback inhibitors of inflammation. Systematic comparison of host RNA sequences incorporated into viral mRNA (“snatched”) against a complete survey of background RNA in the host cell enables an unbiased quantification of over-represented features of snatched host RNAs. We detect preferential snatching of RNAs associated with snRNA transcription and demonstrate that cap-snatching avoids transcripts encoding host ribosomal proteins, which are required by IAV for replication. biorxiv;670919v1/UFIG1F1ufig1 Graphical Abstract(A) Overview of bioinformatics pipeline. (B) Host gene expression reveals that human macrophages exposed to IAV exhibit sustained production of key inflammatory mediators and failure to induce expression of feedback inhibitors of inflammation. (C) Unbiased comparison with total background RNA expression demonstrates that IAV cap-snatching has a strong preference for, and aversion to, different groups of host transcripts.
Digard Paul、Parkinson Nicholas、Bertin Nicolas、Tomoiu Andru、Hayashizaki Yoshihide、Baillie J. Kenneth、Forrest Alistair A.、FANTOM5 Consortium、Summers Kim M.、Wise Helen、Wang Bo、Hume David A.、Clohisey Sara、Carninci Piero
Division of Infection and Immunity, The Roslin Institute, University of EdinburghDivision of Genetics and Genomics, The Roslin Institute, University of Edinburgh||Division of Infection and Immunity, The Roslin Institute, University of EdinburghRIKEN Center for Life Sciences Technologies, RIKEN Yokohama CampusDivision of Genetics and Genomics, The Roslin Institute, University of Edinburgh||Division of Infection and Immunity, The Roslin Institute, University of EdinburghRIKEN Preventive Medicine and Diagnosis Innovation ProgramDivision of Genetics and Genomics, The Roslin Institute, University of EdinburghHarry Perkins Institute of Medical ResearchMater Research Institute-University of Queensland, Translational Research InstituteDivision of Infection and Immunity, The Roslin Institute, University of Edinburgh||Clinical biochemistry, Clock Tower building, Western General HospitalDivision of Genetics and Genomics, The Roslin Institute, University of Edinburgh||Division of Infection and Immunity, The Roslin Institute, University of EdinburghClinical biochemistry, Clock Tower building, Western General HospitalDivision of Genetics and Genomics, The Roslin Institute, University of Edinburgh||Division of Infection and Immunity, The Roslin Institute, University of EdinburghRIKEN Center for Life Sciences Technologies, RIKEN Yokohama Campus
分子生物学细胞生物学遗传学
Digard Paul,Parkinson Nicholas,Bertin Nicolas,Tomoiu Andru,Hayashizaki Yoshihide,Baillie J. Kenneth,Forrest Alistair A.,FANTOM5 Consortium,Summers Kim M.,Wise Helen,Wang Bo,Hume David A.,Clohisey Sara,Carninci Piero.Comprehensive characterisation of molecular host-pathogen interactions in influenza A virus-infected human macrophages[EB/OL].(2025-03-28)[2025-07-25].https://www.biorxiv.org/content/10.1101/670919.点此复制
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