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