title: Induction and suppression of tick cell antiviral RNAi responses by tick-borne flaviviruses.
abstract: Arboviruses are transmitted by distantly related arthropod vectors such as mosquitoes (class Insecta) and ticks (class Arachnida). RNA interference (RNAi) is the major antiviral mechanism in arthropods against arboviruses. Unlike in mosquitoes, tick antiviral RNAi is not understood, although this information is important to compare arbovirus/host interactions in different classes of arbovirus vectos. Using an Ixodes scapularis-derived cell line, key Argonaute proteins involved in RNAi and the response against tick-borne Langat virus (Flaviviridae) replication were identified and phylogenetic relationships characterized. Analysis of small RNAs in infected cells showed the production of virus-derived small interfering RNAs (viRNAs), which are key molecules of the antiviral RNAi response. Importantly, viRNAs were longer (22 nucleotides) than those from other arbovirus vectors and mapped at highest frequency to the termini of the viral genome, as opposed to mosquito-borne flaviviruses. Moreover, tick-borne flaviviruses expressed subgenomic flavivirus RNAs that interfere with tick RNAi. Our results characterize the antiviral RNAi response in tick cells including phylogenetic analysis of genes encoding antiviral proteins, and viral interference with this pathway. This shows important differences in antiviral RNAi between the two major classes of arbovirus vectors, and our data broadens our understanding of arthropod antiviral RNAi.
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow G11 5JR, UK The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK Esther.Schnettler@glasgow.ac.uk.
authors: Esther
authors: E
authors: Schnettler
authors: Faculty of Science, University of South Bohemia and Biology Centre, Institute of Parasitology, Czech Academy of Sciences, 37005 České Budějovice (Budweis), Czech Republic.
authors: Hana
authors: H
authors: Tykalová
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: Mick
authors: M
authors: Watson
authors: Markey Centre for Structural Biology, Department of Biological Sciences, Purdue University, West Lafayette IN 47907, USA.
authors: Mayuri
authors: M
authors: Sharma
authors: Laboratory of Virology, Wageningen University, 6708 PB Wageningen, The Netherlands.
authors: Mark G
authors: MG
authors: Sterken
authors: Institute of Evolutionary Biology and Centre for Infection Immunity and Evolution, University of Edinburgh, EH9 3JT, UK.
authors: Darren J
authors: DJ
authors: Obbard
authors: Institute of Evolutionary Biology and Centre for Infection Immunity and Evolution, University of Edinburgh, EH9 3JT, UK.
authors: Samuel H
authors: SH
authors: Lewis
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow G11 5JR, UK.
authors: Melanie
authors: M
authors: McFarlane
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: Lesley
authors: L
authors: Bell-Sakyi
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: Gerald
authors: G
authors: Barry
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: Sabine
authors: S
authors: Weisheit
authors: Innate Immunity and Pathogenesis Unit, Laboratory of Virology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors: Sonja M
authors: SM
authors: Best
authors: Markey Centre for Structural Biology, Department of Biological Sciences, Purdue University, West Lafayette IN 47907, USA.
authors: Richard J
authors: RJ
authors: Kuhn
authors: Laboratory of Virology, Wageningen University, 6708 PB Wageningen, The Netherlands.
authors: Gorben P
authors: GP
authors: Pijlman
authors: Centre for Immunity, Infection and Evolution, University of Edinburgh, EH9 3JT, UK.
authors: Margo E
authors: ME
authors: Chase-Topping
authors: Unité des Virus Emergents, Faculté de Médicine Timone, 13385 Marseille Cedex 05, France Centre for Hydrology and Ecology, Maclean Building, Oxon OX10 8BB, UK.
authors: Ernest A
authors: EA
authors: Gould
authors: Faculty of Science, University of South Bohemia and Biology Centre, Institute of Parasitology, Czech Academy of Sciences, 37005 České Budějovice (Budweis), Czech Republic.
authors: Libor
authors: L
authors: Grubhoffer
authors: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors: John K
authors: JK
authors: Fazakerley
authors: MRC - University of Glasgow Centre for Virus Research, Glasgow G11 5JR, UK The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK alain.kohl@glasgow.ac.uk.
authors: Alain
authors: A
authors: Kohl
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000502:physiology; D002460:Cell Line; D004669:Encephalitis Viruses, Tick-Borne / Q000235:genetics*; D018884:Ixodes / Q000235:genetics* / Q000821:virology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry; D058727:RNA, Small Untranslated / Q000737:chemistry; D012367:RNA, Viral / Q000737:chemistry; D043244:Ribonuclease III / Q000502:physiology
chemical_list: D060565:Argonaute Proteins; D034741:RNA, Small Interfering; D058727:RNA, Small Untranslated; D012367:RNA, Viral; D043244:Ribonuclease III