Authors

Poornima Parameswaran, Stanford University School of Medicine
Ella Sklan, Stanford University School of Medicine
Courtney Wilkins, University of Arkansas for Medical Sciences
Trever Burgon, Stanford University School of Medicine
Melanie A. Samuel, Washington University School of Medicine in St. Louis
Rui Lu, University of California, Riverside
K. Mark Ansel, University of California, San Francisco
Vigo Heissmeyer, Helmholtz Center Munich German Research Center for Environmental Health
Shirit Einav, Stanford University School of Medicine
William Jackson, Stanford University School of Medicine
Tammy Doukas, Stanford University School of Medicine
Suman Paranjape, University of California, Berkeley
Charlotta Polacek, University of California, Berkeley
Flavia Barreto Dos Santos, University of California, Berkeley
Roxana Jalili, Stanford University School of Medicine
Farbod Babrzadeh, Stanford University School of Medicine
Baback Gharizadeh, Stanford University School of Medicine
Dirk Grimm, Stanford University School of Medicine
Mark Kay, Stanford University School of Medicine
Satoshi Koike, Tokyo Metropolitan Institute of Medical Science
Peter Sarnow, Stanford University School of Medicine
Mostafa Ronaghi, Stanford University School of Medicine
Shou Wei Ding, University of California, Riverside
Eva Harris, University of California, Berkeley
Marie Chow, University of Arkansas for Medical Sciences
Michael S. Diamond, Washington University School of Medicine in St. Louis
Karla Kirkegaard, Stanford University School of Medicine
Jeffrey S. Glenn, Stanford University School of Medicine
Andrew Z. Fire, Stanford University School of Medicine

Document Type

Article

Publication Date

2-1-2010

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. © 2010 Parameswaran et al.

Publication Source (Journal or Book title)

PLoS Pathogens

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