Six RNA Viruses and Forty-One Hosts: Viral Small RNAs and Modulation of Small RNA Repertoires in Vertebrate and Invertebrate Systems
| Autor: | Michael S. Diamond, Poornima Parameswaran, Charlotta Polacek, Rui Lu, Peter Sarnow, Roxana Jalili, Mostafa Ronaghi, Eva Harris, Satoshi Koike, Karla Kirkegaard, Flávia Barreto dos Santos, Trever B. Burgon, K. Mark Ansel, Marie Chow, Baback Gharizadeh, Suman Marie Paranjape, Mark A. Kay, Shirit Einav, Ella H. Sklan, Courtney Wilkins, Tammy Doukas, William T. Jackson, Dirk Grimm, Farbod Babrzadeh, Jeffrey S. Glenn, Melanie A. Samuel, Vigo Heissmeyer, Andrew Fire, Shou-Wei Ding |
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| Přispěvatelé: | Rice, Charles M |
| Rok vydání: | 2010 |
| Předmět: |
Small interfering RNA
Small RNA Immunology/Innate Immunity Microbiology/Innate Immunity Molecular Biology/Bioinformatics RNA Virus Infections RNA interference 2.1 Biological and endogenous factors 2.2 Factors relating to the physical environment Viral Replicon Aetiology RNA Small Interfering Virology/Effects of Virus Infection on Host Gene Expression lcsh:QH301-705.5 Genetics 0303 health sciences 030302 biochemistry & molecular biology Genetics and Genomics/Bioinformatics Argonaute 3. Good health RNA silencing Infectious Diseases Medical Microbiology Vertebrates RNA Viral Infection Biotechnology Research Article lcsh:Immunologic diseases. Allergy RNA Interference innate immunity RNA viruses virus-derived small RNAs Immunology Biology Small Interfering Microbiology 03 medical and health sciences Virology Infectious Diseases/Viral Infections microRNA Animals RNA Viruses Molecular Biology 030304 developmental biology RNA Invertebrates MicroRNAs Good Health and Well Being lcsh:Biology (General) Immunology/Immune Response Parasitology Virology/Host Antiviral Responses lcsh:RC581-607 |
| Zdroj: | PLoS Pathogens, Vol 6, Iss 2, p e1000764 (2010) PLoS pathogens, vol 6, iss 2 PLoS Pathogens PLoS Pathog. 6:e1000764 (2010) |
| ISSN: | 1553-7374 |
| Popis: | We have used multiplexed high-throughput sequencing to characterize changes in small RNA populations that occur during viral infection in animal cells. Small RNA-based mechanisms such as RNA interference (RNAi) have been shown in plant and invertebrate systems to play a key role in host responses to viral infection. Although homologs of the key RNAi effector pathways are present in mammalian cells, and can launch an RNAi-mediated degradation of experimentally targeted mRNAs, any role for such responses in mammalian host-virus interactions remains to be characterized. Six different viruses were examined in 41 experimentally susceptible and resistant host systems. We identified virus-derived small RNAs (vsRNAs) from all six viruses, with total abundance varying from “vanishingly rare” (less than 0.1% of cellular small RNA) to highly abundant (comparable to abundant micro-RNAs “miRNAs”). In addition to the appearance of vsRNAs during infection, we saw a number of specific changes in host miRNA profiles. For several infection models investigated in more detail, the RNAi and Interferon pathways modulated the abundance of vsRNAs. We also found evidence for populations of vsRNAs that exist as duplexed siRNAs with zero to three nucleotide 3′ overhangs. Using populations of cells carrying a Hepatitis C replicon, we observed strand-selective loading of siRNAs onto Argonaute complexes. These experiments define vsRNAs as one possible component of the interplay between animal viruses and their hosts. Author Summary Short RNAs derived from invading viruses with RNA genomes are important components of antiviral immunity in plants, worms and flies. The regulated generation of these short RNAs, and their engagement by the immune apparatus, is essential for inhibiting viral growth in these organisms. Mammals have the necessary protein components to generate these viral-derived short RNAs (“vsRNAs”), raising the question of whether vsRNAs in mammals are a general feature of infections with RNA viruses. Our work with Hepatitis C, Polio, Dengue, Vesicular Stomatitis, and West Nile viruses in a broad host repertoire demonstrates the generality of RNA virus-derived vsRNA production, and the ability of the cellular short RNA apparatus to engage these vsRNAs in mammalian cells. Detailed analyses of vsRNA and host-derived short RNA populations demonstrate both common and virus-specific features of the interplay between viral infection and short RNA populations. The vsRNA populations described in this work represent a novel dimension in both viral pathogenesis and host response. |
| Databáze: | OpenAIRE |
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