title: Six RNA viruses and forty-one hosts: viral small RNAs and modulation of small RNA repertoires in vertebrate and invertebrate systems.
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 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.
authors.affiliation: Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Poornima
authors.initials: P
authors.lastname: Parameswaran
authors.forename: Ella
authors.initials: E
authors.lastname: Sklan
authors.forename: Courtney
authors.initials: C
authors.lastname: Wilkins
authors.forename: Trever
authors.initials: T
authors.lastname: Burgon
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Samuel
authors.forename: Rui
authors.initials: R
authors.lastname: Lu
authors.forename: K Mark
authors.initials: KM
authors.lastname: Ansel
authors.forename: Vigo
authors.initials: V
authors.lastname: Heissmeyer
authors.forename: Shirit
authors.initials: S
authors.lastname: Einav
authors.forename: William
authors.initials: W
authors.lastname: Jackson
authors.forename: Tammy
authors.initials: T
authors.lastname: Doukas
authors.forename: Suman
authors.initials: S
authors.lastname: Paranjape
authors.forename: Charlotta
authors.initials: C
authors.lastname: Polacek
authors.forename: Flavia Barreto
authors.initials: FB
authors.lastname: dos Santos
authors.forename: Roxana
authors.initials: R
authors.lastname: Jalili
authors.forename: Farbod
authors.initials: F
authors.lastname: Babrzadeh
authors.forename: Baback
authors.initials: B
authors.lastname: Gharizadeh
authors.forename: Dirk
authors.initials: D
authors.lastname: Grimm
authors.forename: Mark
authors.initials: M
authors.lastname: Kay
authors.forename: Satoshi
authors.initials: S
authors.lastname: Koike
authors.forename: Peter
authors.initials: P
authors.lastname: Sarnow
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ronaghi
authors.forename: Shou-Wei
authors.initials: SW
authors.lastname: Ding
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
authors.forename: Marie
authors.initials: M
authors.lastname: Chow
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.forename: Karla
authors.initials: K
authors.lastname: Kirkegaard
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Glenn
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Fire
mesh_terms: D000818:Animals; D007448:Invertebrates / Q000235:genetics / Q000821:virology*; D035683:MicroRNAs; D012327:RNA Virus Infections / Q000235:genetics*; D012328:RNA Viruses; D034741:RNA, Small Interfering; D012367:RNA, Viral / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics* / Q000821:virology*
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering; D012367:RNA, Viral