Induction and suppression of tick cell antiviral RNAi responses by tick-borne flaviviruses

被引:110
作者
Schnettler, Esther [1 ,2 ,3 ]
Tykalova, Hana [4 ,5 ]
Watson, Mick [2 ,3 ]
Sharma, Mayuri [6 ]
Sterken, Mark G. [7 ]
Obbard, Darren J. [8 ,9 ]
Lewis, Samuel H. [8 ,9 ]
McFarlane, Melanie [1 ]
Bell-Sakyi, Lesley [2 ,3 ]
Barry, Gerald [2 ,3 ]
Weisheit, Sabine [2 ,3 ]
Best, Sonja M. [10 ]
Kuhn, Richard J. [6 ]
Pijlman, Gorben P. [7 ]
Chase-Topping, Margo E. [11 ]
Gould, Ernest A. [12 ,13 ]
Grubhoffer, Libor [4 ,5 ]
Fazakerley, John K. [2 ,3 ]
Kohl, Alain [1 ,2 ,3 ]
机构
[1] MRC Univ Glasgow Ctr Virus Res, Glasgow G11 5JR, Lanark, Scotland
[2] Univ Edinburgh, Roslin Inst, Easter Bush EH25 9RG, Midlothian, Scotland
[3] Univ Edinburgh, Royal Dick Sch Vet Studies, Easter Bush EH25 9RG, Midlothian, Scotland
[4] Univ South Bohemia, Fac Sci, Ceske Budejovice 37005, Budweis, Czech Republic
[5] Czech Acad Sci, Inst Parasitol, Ctr Biol, Ceske Budejovice 37005, Budweis, Czech Republic
[6] Purdue Univ, Dept Biol Sci, Markey Ctr Struct Biol, W Lafayette, IN 47907 USA
[7] Wageningen Univ, Lab Virol, NL-6708 PB Wageningen, Netherlands
[8] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland
[9] Univ Edinburgh, Ctr Infect Immun & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland
[10] NIAID, Innate Immun & Pathogenesis Unit, Virol Lab, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT 59840 USA
[11] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland
[12] Fac Med Timone, Unite Virus Emergents, F-13385 Marseille 05, France
[13] Ctr Hydrol & Ecol, Wallingford OX10 8BB, Oxon, England
基金
英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院; 英国生物技术与生命科学研究理事会;
关键词
FOREST-VIRUS REPLICON; INTERFERENCE; IMMUNITY; IDENTIFICATION; REPLICATION; ALPHAVIRUS; ORIGIN; INFECTION; EVOLUTION; PATHWAY;
D O I
10.1093/nar/gku657
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Arboviruses are transmitted by distantly related arthropod vectors such as mosquitoes (class In-secta) 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.
引用
收藏
页码:9436 / 9446
页数:11
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