In RNA interference (RNAi), long double-stranded RNA is cleaved by the Dicer endonuclease into small interfering RNAs (siRNAs), which guide degradation of complementary RNAs. While RNAi mediates antiviral innate immunity in plants and many invertebrates, vertebrates have adopted a sequence-independent response and their Dicer produces siRNAs inefficiently because it is adapted to process small hairpin microRNA precursors in the gene-regulating microRNA pathway. Mammalian endogenous RNAi is thus a rudimentary pathway of unclear significance. To investigate its antiviral potential, we modified the mouse Dicer locus to express a truncated variant (DicerΔHEL1) known to stimulate RNAi and we analyzed how DicerΔHEL1/wt mice respond to four RNA viruses: coxsackievirus B3 and encephalomyocarditis virus from Picornaviridae; tick-borne encephalitis virus from Flaviviridae; and lymphocytic choriomeningitis virus (LCMV) from Arenaviridae. Increased Dicer activity in DicerΔHEL1/wt mice did not elicit any antiviral effect, supporting an insignificant antiviral function of endogenous mammalian RNAi in vivo. However, we also observed that sufficiently high expression of DicerΔHEL1 suppressed LCMV in embryonic stem cells and in a transgenic mouse model. Altogether, mice with increased Dicer activity offer a new benchmark for identifying and studying viruses susceptible to mammalian RNAi in vivo.

In RNA interference (RNAi), the enzyme Dicer cuts long double-stranded RNA into small interfering RNAs that degrade matching RNAs. RNAi is a key antiviral defense in plants and invertebrates but vertebrates evolved a principally different antiviral defense. The authors genetically modified Dicer in mice to activate RNAi in mammals. These modified mice were tested against four RNA viruses but showed no significant antiviral response. However, further increased expression of modified Dicer did suppress one virus (lymphocytic choriomeningitis virus) in embryonic stem cells and in a transgenic mouse model, suggesting that some viruses might be sensitive to increased RNAi activity in mammals.

• MeSH
• DEAD-box RNA Helicases genetics   metabolism   MeSH
• RNA, Small Interfering genetics   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Immunity, Innate * genetics   MeSH
• Ribonuclease III * genetics   metabolism   MeSH
• RNA Interference * MeSH
• Encephalomyocarditis virus genetics   immunology   MeSH
• Lymphocytic choriomeningitis virus immunology   genetics   MeSH
• Encephalitis Viruses, Tick-Borne genetics   immunology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• DEAD-box RNA Helicases MeSH
• Dicer1 protein, mouse MeSH Browser
• RNA, Small Interfering MeSH
• Ribonuclease III * MeSH

Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection in vitro in human primary neurons (high cytopathic effect) and astrocytes (low cytopathic effect). Infection with severe but not mild TBEV strain resulted in a high neuronal death rate. In comparison, infection with either of TBEV strains in human astrocytes did not. Differential expression and splicing analyses with an in silico prediction of miRNA/mRNA/lncRNA/vd-sRNA networks found significant changes in inflammatory and immune response pathways, nervous system development and regulation of mitosis in TBEV Hypr-infected neurons. Candidate mechanisms responsible for the aforementioned phenomena include specific regulation of host mRNA levels via differentially expressed miRNAs/lncRNAs or vd-sRNAs mimicking endogenous miRNAs and virus-driven modulation of host pre-mRNA splicing. We suggest that these factors are responsible for the observed differences in the virulence manifestation of both TBEV strains in different cell lines. This work brings the first complex overview of alterations in the transcriptome of human astrocytes and neurons during the infection by two TBEV strains of different virulence. The resulting data could serve as a starting point for further studies dealing with the mechanism of TBEV-host interactions and the related processes of TBEV pathogenesis.

• Keywords
• A3SS, alternative 3′ splice site, A5SS, alternative 5′ splice site, ACACA, Acetyl-CoA Carboxylase Alpha, AKR1C2, Aldo-Keto Reductase Family 1 Member C2, ANKS1A, Ankyrin Repeat And Sterile Alpha Motif Domain Containing 1A, ANOS1, Anosmin 1, AOX1, Aldehyde Oxidase 1, APOBEC3G, Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3G, APOL1/6, Apolipoprotein L1/6, ARID2, AT-Rich Interaction Domain 2, AUTS2, Activator Of Transcription And Developmental Regulator AUTS2, Alternative splicing, Astrocytes, BCL11B, BAF Chromatin Remodeling Complex Subunit BCL11B, BCL9L, BCL9 Transcription Coactivator-like, BDKRB2, Bradykinin Receptor B2, BDNF, Brain Derived Neurotrophic Factor, BEND3, BEN Domain Containing 3, BSA, bovine serum albumin, BST2, Bone Marrow Stromal Cell Antigen 2, CALB1, Calbindin 1, CAMK2A, Calcium/Calmodulin Dependent Protein Kinase II Alpha, CD, complement determinant, CDKN1C, Cyclin Dependent Kinase Inhibitor 1C, CFAP61, Cilia And Flagella Associated Protein 61, CHRNA3, Cholinergic Receptor Nicotinic Alpha 3 Subunit, CHRNB4, Cholinergic Receptor Nicotinic Beta 4 Subunit, CLIC5, Chloride Intracellular Channel 5, CMPK2, Cytidine/Uridine Monophosphate Kinase 2, CNS, central nervous system, CNTN2, Contactin 2, CREG2, Cellular Repressor Of E1A Stimulated Genes 2, CXADR, Coxsackievirus B-Adenovirus Receptor, CYYR1, Cysteine And Tyrosine Rich 1, DACH1, Dachshund Family Transcription Factor 1, DAPI, diamidino-2-phenylindole, DCC, Netrin 1 Receptor, DCX, Doublecortin, DDX60, DExD/H-Box Helicase 60, DDX60L, DExD/H-Box 60 Like, DE, differentially expressed, DENV, Dengue virus, DIRAS2, DIRAS Family GTPase 2, DLX1/5/6, Distal-Less Homeobox 1/5/6, DNMT3B, DNA Methyltransferase 3 Beta, DPYSL2, Dihydropyrimidinase Like 2, EBF1, EBF Transcription Factor 1, EGF, Epidermal Growth Factor, ELAVL2/4, ELAV Like RNA Binding Protein 2/4, EPHB1, EPH Receptor B1, EPSTI1, Epithelial Stromal Interaction 1, ERBB4, Erb-B2 Receptor Tyrosine Kinase 4, ES, exon skipping, ESRRG, Estrogen Related Receptor Gamma, FGFb, Fibroblast Growth Factor 2, FPKM, Fragments Per Kilobase of transcript per Million mapped reads, FUT9, Fucosyltransferase 9, G2E3, G2/M−Phase Specific E3 Ubiquitin Protein Ligase, GABRG2, Gamma-Aminobutyric Acid Type A Receptor Subunit Gamma 2, GAPDH, Glyceraldehyde-3-Phosphate Dehydrogenase, GAS2L3, Growth Arrest Specific 2 Like 3, GAS7, Growth Arrest Specific 7, GATAD2B, GATA Zinc Finger Domain Containing 2B, GFAP, Glial Fibrillary Acidic Protein, GIPC2, GIPC PDZ Domain Containing Family Member 2, GLRA2, Glycine Receptor Alpha 2, GNG2, G Protein Subunit Gamma 2, GO, gene ontology, GOLGA4, Golgin A4, GRIN2A, Glutamate Ionotropic Receptor NMDA Type Subunit 2A, GSEA, gene set enrichment analysis, HERC5/6, HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 5/6, HEYL, Hes Related Family BHLH Transcription Factor With YRPW Motif Like, HPRT1, Hypoxanthine Phosphoribosyltransferase 1, HS, hot-spot, HSPA6, Heat Shock Protein Family A (Hsp70) Member 6, HUDD (ELAV4), Hu-Antigen D/ELAV Like Neuron-Specific RNA Binding Protein 4, IFI6, Interferon Alpha Inducible Protein 6, IFIH1 (MDA5), Interferon Induced With Helicase C Domain 1/Melanoma Differentiation-Associated Protein 5, IFIT1-3, Interferon Induced Protein With Tetratricopeptide Repeats 1–3, IFITM1/2, Interferon Induced Transmembrane Protein 1/2, IFN, interferon, IGB, Integrated Genome Browser, IL6, Interleukin 6, IR, intron retention, ISG20, Interferon Stimulated Exonuclease Gene 20, ISGF3, Interferon-Stimulated Gene Factor 3 Gamma, ISGs, interferon-stimulated genes, JEV, Japanese encephalitis virus, KCND2, Potassium Voltage-Gated Channel Subfamily D Member 2, KCNK10, Potassium Two Pore Domain Channel Subfamily K Member 10, KCNS2, Potassium Voltage-Gated Channel Modifier Subfamily S Member 2, KIT, KIT Proto-Oncogene, Receptor Tyrosine Kinase, KLHDC8A, Kelch Domain Containing 8A, KLHL13, Kelch Like Family Member 13, KRR1, KRR1 Small Subunit Processome Component Homolog, LCOR, Ligand Dependent Nuclear Receptor Corepressor, LEKR1, Leucine, Glutamate And Lysine Rich 1, LGI1, Leucine Rich Glioma Inactivated 1, LRRTM3, Leucine Rich Repeat Transmembrane Neuronal 3, LSV, local splicing variation, LUZP2, Leucine Zipper Protein 2, MAN1A1, Mannosidase Alpha Class 1A Member 1, MAP2, Microtubule Associated Protein 2, MBNL2, Muscleblind Like Splicing Regulator 2, MCTP1, Multiple C2 And Transmembrane Domain Containing 1, MMP13, Matrix Metallopeptidase 13, MN1, MN1 Proto-Oncogene, Transcriptional Regulator, MOI, multiplicity of infection, MTUS2, Microtubule Associated Scaffold Protein 2, MX2, MX Dynamin Like GTPase 2, MYCN, MYCN Proto-Oncogene, BHLH Transcription Factor, NAV1, Neuron Navigator 1, NCAM1, Neural Cell Adhesion Molecule 1, NDRG4, N-Myc Downstream-Regulated Gene 4 Protein, NEK7, NIMA Related Kinase 7, NFASC, Neurofascin, NKAIN1, Sodium/Potassium Transporting ATPase Interacting 1, NMI, N-Myc And STAT Interactor 2, NRAP, Nebulin Related Anchoring Protein, NRARP, NOTCH Regulated Ankyrin Repeat Protein, NREP, Neuronal Regeneration Related Protein, NRN1, Neuritin 1, NS3, flaviviral non-structural protein 3, NXPH2, Neurexophilin 2, NYNRIN, NYN Domain And Retroviral Integrase Containing, Neurons, Neuropathogenesis, OAS, 2′-5′-Oligoadenylate Synthetase, OASL, 2′-5′-Oligoadenylate Synthetase Like, ONECUT2, ONECUT-2 Homeodomain Transcription Factor, OPCML, Opioid Binding Protein/Cell Adhesion Molecule Like, OTX2, Orthodenticle Homeobox 2, PBS, phosphate buffer saline, PBX1, Pre-B-Cell Leukemia Transcription Factor 1, PCDH18/20, Protocadherin 18/20, PFKFB3, 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3, PIK3C2B, Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta, PIP4P2, Phosphatidylinositol-4,5-Bisphosphate 4-Phosphatase 2, PLCH1, Phospholipase C Eta 1, POU3F4, Brain-Specific Homeobox/POU Domain Protein 4, PPM1L, Protein Phosphatase, Mg2+/Mn2+ Dependent 1L, PPP1R17, Protein Phosphatase 1 Regulatory Subunit 17, PRDM12, PR Domain Zinc Finger Protein 12, PSI, percent selective index, PSRC1, Proline And Serine Rich Coiled-Coil 1, PTPN5, Protein Tyrosine Phosphatase Non-Receptor Type 5, PTPRH, Protein Tyrosine Phosphatase Receptor Type H, RAPGEF5, Rap Guanine Nucleotide Exchange Factor 5, RBFOX1, RNA Binding Fox-1 Homolog 1, RIG-I (DDX58), Retinoic Acid-Inducible Gene 1 Protein, RNF212, Ring Finger Protein 212, RNVU1, RNA, Variant U1 Small Nuclear, RSAD2, Radical S-Adenosyl Methionine Domain Containing 2, RTL8B, Retrotransposon Gag Like 8B, Response to infection, SAMD9, Sterile Alpha Motif Domain Containing 9, SEMA3E, Semaphorin 3E, SH3TC2, SH3 Domain And Tetratricopeptide Repeats 2, SHF, Src Homology 2 Domain Containing F, SHISAL1, Shisa Like 1, SIAH3, Siah E3 Ubiquitin Protein Ligase Family Member 3, SIRPA, Signal Regulatory Protein Alpha, SLITRK5, SLIT And NTRK Like Family Member 5, SNP, single-nucleotide polymorphism, SOGA1, Suppressor Of Glucose, Autophagy Associated 1, SPSB4, SplA/Ryanodine Receptor Domain And SOCS Box Containing 4, ST6GAL1, ST6 Beta-Galactoside Alpha-2,6-Sialyltransferase 1, TBC1D30, TBC1 Domain Family Member 30, TBEV, Tick-borne encephalitis virus, TFAP2A, Transcription Factor AP-2 Alpha, TFAP2B, Transcription Factor AP-2 Beta, THSD7A, Thrombospondin Type 1 Domain Containing 7A, THUMPD2, THUMP Domain-Containing Protein 2/SAM-Dependent Methyltransferase, TIPARP, TCDD Inducible Poly(ADP-Ribose) Polymerase, TM4SF18, Transmembrane 4 L Six Family Member 18, TMC8, Transmembrane Channel Like 6, TMEM229B, Transmembrane Protein 229B, TMTC1, Transmembrane O-Mannosyltransferase Targeting Cadherins 1, TNFSF10, TNF Superfamily Member 10, TRHDE, Thyrotropin Releasing Hormone Degrading Enzyme, TRIM38, Tripartite Motif Containing 38, TSHZ1, Teashirt Zinc Finger Homeobox 1, Tick-borne encephalitis virus, Transcriptomics, USP18, Ubiquitin Specific Peptidase 18/ISG15-Specific-Processing Protease, UTR, untranslated region, UTS2R, Urotensin 2 Receptor, WNV, West Nile virus, XAF1, XIAP Associated Factor 1, XRN1, 5′-3′ Exoribonuclease 1, ZIKV, Zika virus, ZMAT3, Zinc Finger Matrin-Type 3, ZMYM5, Zinc Finger MYM-Type Containing 5, ZNF124, Zinc Finger Protein 124, ZNF730, Zinc Finger Protein 730, gRNA, genomic TBEV RNA, hNSC, human neural stem cells, lncRNA, long non-coding RNA, mRNA, messenger RNA, miRNA, miRNA, micro RNA, ncRNA, non-coding RNA, pc-mRNA, protein-coding mRNA, qRT-PCR, quantitative reverse transcription real-time PCR, snRNP, small nuclear ribonucleoproteins, vd-sRNA, virus-derived small RNA,
• Publication type
• Journal Article MeSH

Up to 170 tick-borne viruses (TBVs) have been identified to date. However, there is a paucity of information regarding TBVs and their interaction with respective vectors, limiting the development of new effective and urgently needed control methods. To overcome this gap of knowledge, it is essential to reproduce transmission cycles under controlled laboratory conditions. In this study we assessed an artificial feeding system (AFS) and an immersion technique (IT) to infect Ixodes ricinus ticks with tick-borne encephalitis (TBE) and Kemerovo (KEM) virus, both known to be transmitted predominantly by ixodid ticks. Both methods permitted TBEV acquisition by ticks and we further confirmed virus trans-stadial transmission and onward transmission to a vertebrate host. However, only artificial feeding system allowed to demonstrate both acquisition by ticks and trans-stadial transmission for KEMV. Yet we did not observe transmission of KEMV to mice (IFNAR-/- or BALB/c). Artificial infection methods of ticks are important tools to study tick-virus interactions. When optimally used under laboratory settings, they provide important insights into tick-borne virus transmission cycles.

• MeSH
• Arachnid Vectors physiology   virology   MeSH
• Host-Pathogen Interactions MeSH
• Ixodes physiology   virology   MeSH
• Encephalitis, Tick-Borne transmission   virology   MeSH
• Humans MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Orbivirus physiology   MeSH
• Reoviridae Infections transmission   virology   MeSH
• Virology methods   MeSH
• Encephalitis Viruses, Tick-Borne physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH
• Research Support, Non-U.S. Gov't MeSH

Ticks are ectoparasitic arthropods that necessarily feed on the blood of their vertebrate hosts. The success of blood acquisition depends on the pharmacological properties of tick saliva, which is injected into the host during tick feeding. Saliva is also used as a vehicle by several types of pathogens to be transmitted to the host, making ticks versatile vectors of several diseases for humans and other animals. When a tick feeds on an infected host, the pathogen reaches the gut of the tick and must migrate to its salivary glands via hemolymph to be successfully transmitted to a subsequent host during the next stage of feeding. In addition, some pathogens can colonize the ovaries of the tick and be transovarially transmitted to progeny. The tick immune system, as well as the immune system of other invertebrates, is more rudimentary than the immune system of vertebrates, presenting only innate immune responses. Although simpler, the large number of tick species evidences the efficiency of their immune system. The factors of their immune system act in each tick organ that interacts with pathogens; therefore, these factors are potential targets for the development of new strategies for the control of ticks and tick-borne diseases. The objective of this review is to present the prevailing knowledge on the tick immune system and to discuss the challenges of studying tick immunity, especially regarding the gaps and interconnections. To this end, we use a comparative approach of the tick immune system with the immune system of other invertebrates, focusing on various components of humoral and cellular immunity, such as signaling pathways, antimicrobial peptides, redox metabolism, complement-like molecules and regulated cell death. In addition, the role of tick microbiota in vector competence is also discussed.

• Keywords
• cell-mediated immunity, immune signaling pathway, immune system, microbiota, tick-borne pathogen,
• MeSH
• Immunity, Cellular * MeSH
• Immunity, Humoral * MeSH
• Host-Parasite Interactions MeSH
• Ticks immunology   metabolism   MeSH
• Humans MeSH
• Tick-Borne Diseases immunology   metabolism   transmission   MeSH
• Salivary Glands immunology   metabolism   MeSH
• Saliva immunology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Canonical RNAi, one of the so-called RNA-silencing mechanisms, is defined as sequence-specific RNA degradation induced by long double-stranded RNA (dsRNA). RNAi occurs in four basic steps: (i) processing of long dsRNA by RNase III Dicer into small interfering RNA (siRNA) duplexes, (ii) loading of one of the siRNA strands on an Argonaute protein possessing endonucleolytic activity, (iii) target recognition through siRNA basepairing, and (iv) cleavage of the target by the Argonaute's endonucleolytic activity. This basic pathway diversified and blended with other RNA silencing pathways employing small RNAs. In some organisms, RNAi is extended by an amplification loop employing an RNA-dependent RNA polymerase, which generates secondary siRNAs from targets of primary siRNAs. Given the high specificity of RNAi and its presence in invertebrates, it offers an opportunity for highly selective pest control. The aim of this text is to provide an introductory overview of key mechanistic aspects of RNA interference for understanding its potential and constraints for its use in pest control.

• Keywords
• RNAi, argonaute, dicer, dsRNA, miRNA, off-targeting,
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into a major public health concern. Little is currently known about the evolution and biology of ZIKV and the factors that contribute to the associated pathogenesis. Determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative processes and virus-host interactions. METHODOLOGY/PRINCIPAL FINDINGS: We obtained a ZIKV isolate from a patient who presented with classical ZIKV-associated symptoms, and used high throughput sequencing and other molecular biology approaches to determine its full genome sequence, including non-coding regions. Genome regions were characterized and compared to the sequences of other isolates where available. Furthermore, we identified a subgenomic flavivirus RNA (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced type I interferon induction, with a lesser effect on MDA-5 mediated action. CONCLUSIONS/SIGNIFICANCE: The full-length genome sequence including non-coding regions of a South American ZIKV isolate from a patient with classical symptoms will support efforts to develop genetic tools for this virus. Detection of sfRNA that counteracts interferon responses is likely to be important for further understanding of pathogenesis and virus-host interactions.

• MeSH
• A549 Cells MeSH
• DEAD Box Protein 58 metabolism   MeSH
• Disease Outbreaks MeSH
• Phylogeny MeSH
• Genome, Viral * MeSH
• Zika Virus Infection virology   MeSH
• Host-Pathogen Interactions MeSH
• Interferon Type I antagonists & inhibitors   biosynthesis   genetics   MeSH
• Humans MeSH
• Virus Replication MeSH
• RNA, Viral genetics   isolation & purification   MeSH
• Vero Cells MeSH
• Zika Virus genetics   isolation & purification   pathogenicity   physiology   MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Brazil epidemiology   MeSH
• Names of Substances
• DEAD Box Protein 58 MeSH
• Interferon Type I MeSH
• RNA, Viral MeSH

BACKGROUND: Ixodid ticks are important vectors of a wide variety of viral, bacterial and protozoan pathogens of medical and veterinary importance. Although several studies have elucidated tick responses to bacteria, little is known about the tick response to viruses. To gain insight into the response of tick cells to flavivirus infection, the transcriptomes and proteomes of two Ixodes spp cell lines infected with the flavivirus tick-borne encephalitis virus (TBEV) were analysed. METHODS: RNA and proteins were isolated from the Ixodes scapularis-derived cell line IDE8 and the Ixodes ricinus-derived cell line IRE/CTVM19, mock-infected or infected with TBEV, on day 2 post-infection (p.i.) when virus production was increasing, and on day 6 p.i. when virus production was decreasing. RNA-Seq and mass spectrometric technologies were used to identify changes in abundance of, respectively, transcripts and proteins. Functional analyses were conducted on selected transcripts using RNA interference (RNAi) for gene knockdown in tick cells infected with the closely-related but less pathogenic flavivirus Langat virus (LGTV). RESULTS: Differential expression analysis using DESeq resulted in totals of 43 and 83 statistically significantly differentially-expressed transcripts in IDE8 and IRE/CTVM19 cells, respectively. Mass spectrometry detected 76 and 129 statistically significantly differentially-represented proteins in IDE8 and IRE/CTVM19 cells, respectively. Differentially-expressed transcripts and differentially-represented proteins included some that may be involved in innate immune and cell stress responses. Knockdown of the heat-shock proteins HSP90, HSP70 and gp96, the complement-associated protein Factor H and the protease trypsin resulted in increased LGTV replication and production in at least one tick cell line, indicating a possible antiviral role for these proteins. Knockdown of RNAi-associated proteins Argonaute and Dicer, which were included as positive controls, also resulted in increased LGTV replication and production in both cell lines, confirming their role in the antiviral RNAi pathway. CONCLUSIONS: This systems biology approach identified several molecules that may be involved in the tick cell innate immune response against flaviviruses and highlighted that ticks, in common with other invertebrate species, have other antiviral responses in addition to RNAi.

• MeSH
• Arachnid Vectors * genetics   metabolism   virology   MeSH
• Cell Line MeSH
• Gene Knockdown Techniques MeSH
• Ixodes * genetics   immunology   metabolism   virology   MeSH
• Immunity, Innate MeSH
• Proteomics * MeSH
• RNA Interference MeSH
• Gene Expression Profiling * MeSH
• Encephalitis Viruses, Tick-Borne immunology   physiology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Tudor staphylococcal nuclease (Tudor-SN) and Argonaute (Ago) are conserved components of the basic RNA interference (RNAi) machinery with a variety of functions including immune response and gene regulation. The RNAi machinery has been characterized in tick vectors of human and animal diseases but information is not available on the role of Tudor-SN in tick RNAi and other cellular processes. Our hypothesis is that tick Tudor-SN is part of the RNAi machinery and may be involved in innate immune response and other cellular processes. To address this hypothesis, Ixodes scapularis and I. ricinus ticks and/or cell lines were used to annotate and characterize the role of Tudor-SN in dsRNA-mediated RNAi, immune response to infection with the rickettsia Anaplasma phagocytophilum and the flaviviruses TBEV or LGTV and tick feeding. The results showed that Tudor-SN is conserved in ticks and involved in dsRNA-mediated RNAi and tick feeding but not in defense against infection with the examined viral and rickettsial pathogens. The effect of Tudor-SN gene knockdown on tick feeding could be due to down-regulation of genes that are required for protein processing and blood digestion through a mechanism that may involve selective degradation of dsRNAs enriched in G:U pairs that form as a result of adenosine-to-inosine RNA editing. These results demonstrated that Tudor-SN plays a role in tick RNAi pathway and feeding but no strong evidence for a role in innate immune responses to pathogen infection was found.

• MeSH
• Anaplasma phagocytophilum pathogenicity   MeSH
• Cell Line MeSH
• Flavivirus pathogenicity   MeSH
• Phylogeny MeSH
• Nuclear Proteins genetics   metabolism   MeSH
• Ixodes genetics   parasitology   virology   MeSH
• Conserved Sequence MeSH
• Cricetinae MeSH
• Molecular Sequence Data MeSH
• RNA Interference * MeSH
• Amino Acid Sequence MeSH
• Transcriptome MeSH
• Animals MeSH
• Check Tag
• Cricetinae MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Nuclear Proteins MeSH