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

Poornima Parameswaran, Ella Sklan, Courtney Wilkins, Trever Burgon, Melanie A. Samuel, Rui Lu, K. Mark Ansel, Vigo Heissmeyer, Shirit Einav, William Jackson, Tammy Doukas, Suman Paranjape, Charlotta Polacek, Flavia Barreto Dos Santos, Roxana Jalili, Farbod Babrzadeh, Baback Gharizadeh, Dirk Grimm, Mark Kay, Satoshi KoikePeter Sarnow, Mostafa Ronaghi, Shou Wei Ding, Eva Harris, Marie Chow, Michael S. Diamond, Karla Kirkegaard, Jeffrey S. Glenn, Andrew Z. Fire

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

Abstract

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 39 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.

Original languageEnglish
Article numbere1000764
JournalPLoS pathogens
Volume6
Issue number2
DOIs
StatePublished - Feb 2010

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