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Parameswaran, P.* ; Sklan, E.* ; Wilkins, C.* ; Burgon, T.* ; Samuel, M.A.* ; Lu, R.* ; Ansel, K.M.* ; Heissmeyer, V. ; Einav, S.* ; Jackson, W.* ; Douka, T.* ; Paranjape, S.* ; Polacek, C.* ; dos Santos, F.B.* ; Jalili, R.* ; Babrzadeh, F. ; Gharizadeh, B.* ; Grimm, D.* ; Kay, M.* ; Koike, S.* ; Sarnow, P.* ; Ronaghi, M.* ; Ding, S.W.* ; Harris, E.* ; Chow, M.* ; Diamond, M.S.* ; Kirkegaard, K.* ; Glenn, J.S.* ; Fire, A.Z.*

Six RNA viruses and forty-one hosts: Viral small RNAs and modulation of small RNA repertoires in vertebrate and invertebrate systems.

PLoS Pathog. 6:e1000764 (2010)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords RNA Interference; innate immunity; RNA viruses; virus-derived small RNAs; HEPATITIS-C VIRUS; DOUBLE-STRANDED-RNA; VESICULAR STOMATITIS-VIRUS; INDUCED SILENCING COMPLEX; INFLUENZA-A VIRUS; CAENORHABDITIS-ELEGANS; ANTIVIRAL IMMUNITY; DROSOPHILA-MELANOGASTER; MAMMALIAN-CELLS; CELLULAR MICRORNAS
Language english
Publication Year 2010
HGF-reported in Year 2010
ISSN (print) / ISBN 1553-7366
e-ISSN 1553-7374
Journal PLoS Pathogens
Quellenangaben Volume: 6, Issue: 2, Pages: , Article Number: e1000764 Supplement: ,
Publisher Public Library of Science (PLoS)
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)
Research Unit Molecular Immune Regulation (AMIR)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s) G-551000-001
G-501792-001
PubMed ID 20169186
DOI 10.1371/journal.ppat.1000764
WOS ID 000275295900016
Scopus ID 77649239548
Erfassungsdatum 2010-02-12
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