Capillary feeding of specific dsRNA induces silencing of the <i>isac</i> gene in nymphal <i>Ixodes scapularis</i> ticks

Soares, Carlos A. G.; Lima, C. M. R.; Dolan, Marc C.; Piesman, Joseph; Beard, Charles B.; Zeidner, Nordin S.

doi:10.1111/j.1365-2583.2005.00575.x

Cited by 81 publications

(68 citation statements)

References 62 publications

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“…Salp20 is a member of the ILP family, containing at least 49 members (7,8,10,11). In addition to Salp20, several members of this family, specifically Isac, Irac I, Irac II, S20Lclone 12, and S20Lclone 2, inhibit the alternative pathway by decay acceleration of the C3 convertase (9 -11) (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…One property of tick saliva is inhibition of the alternative complement pathway (4 -6). Ixodes scapularis anti-complement protein (Isac) 3 and salivary protein 20 (Salp20), and Ixodes ricinus anti-complement proteins I and II (Irac I and Irac II) are members of a large family of homologous proteins, referred to as the Isac-like protein (ILP) family, that specifically inhibit the alternative pathway by dissociating the components of the C3 convertase, C3b, and cleaved factor B (Bb) (7)(8)(9)(10)(11). While preventing the activation of the alternative pathway, Salp20 also protects Borrelia garinii from complement-mediated killing by normal human serum (NHS) (10), suggesting these anti-complement proteins facilitate tick feeding as well as pathogen transmission and survival.…”

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confidence: 99%

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A Novel Mechanism of Complement Inhibition Unmasked by a Tick Salivary Protein That Binds to Properdin

Tyson

Elkins

Silva

2008

The Journal of Immunology

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Ixodes scapularis salivary protein 20 (Salp20) is a member of the Ixodes scapularis anti-complement protein-like family of tick salivary proteins that inhibit the alternative complement pathway. In this study, we demonstrate that the target of Salp20 is properdin. Properdin is a natural, positive regulator of the alternative pathway that binds to the C3 convertase, stabilizing the molecule. Salp20 directly bound to and displaced properdin from the C3 convertase. Displacement of properdin accelerated the decay of the C3 convertase, leading to inhibition of the alternative pathway. S20NS is distinct from known decay accelerating factors, such as decay accelerating factor, complement receptor 1, and factor H, which directly interact with either C3b or cleaved factor B.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A Novel Mechanism of Complement Inhibition Unmasked by a Tick Salivary Protein That Binds to Properdin

Tyson

Elkins

Silva

2008

The Journal of Immunology

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“…Thus dsRNA can enter the animal from the environment. RNAi triggered by environmental exposure to dsRNA has also been documented in planaria, moth, tick, hydra, and numerous parasitic nematodes (10)(11)(12)(13)(14)(15), suggesting that many invertebrates possess mechanisms to transport sequence nonspecific dsRNA into and between cells.…”

mentioning

confidence: 99%

Caenorhabditis elegans SID-2 is required for environmental RNA interference

Winston

Sutherlin

Wright

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

289

322

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In plants and in the nematode Caenorhabditis elegans, an RNAi signal can trigger gene silencing in cells distant from the site where silencing is initiated. In plants, this signal is known to be a form of dsRNA, and the signal is most likely a form of dsRNA in C. elegans as well. Furthermore, in C. elegans, dsRNA present in the environment or expressed in ingested bacteria is sufficient to trigger RNAi (environmental RNAi). Ingestion and soaking delivery of dsRNA has also been described for other invertebrates. Here we report the identification and characterization of SID-2, an intestinal luminal transmembrane protein required for environmental RNAi in C. elegans. SID-2, when expressed in the environmental RNAi defective species Caenorhabditis briggsae, confers environmental RNAi.dsRNA ͉ transmembrane ͉ intestine lumen T ranslocation of nucleic acids across cellular membranes is associated with viral infection, bacterial conjugation, and transport of nuclear encoded tRNAs into mitochondria (1-3). In these cases, specific machinery acts to translocate a specific RNA or DNA across one or more membranous barriers. However, observations in plants suggest the routine intercellular transport of cellular mRNAs as well as processed, likely short, dsRNAs associated with RNAi-related phenomena that mediate systemic virus resistance (4, 5). In the nematode Caenorhabditis elegans, RNA-induced gene silencing is also systemic, spreading from the site of injection or expression to silence the targeted gene throughout the animal and in its progeny (6, 7). Furthermore, RNAi can be initiated by soaking animals in solutions of dsRNA or feeding worms bacteria expressing dsRNA (8, 9). Thus dsRNA can enter the animal from the environment. RNAi triggered by environmental exposure to dsRNA has also been documented in planaria, moth, tick, hydra, and numerous parasitic nematodes (10-15), suggesting that many invertebrates possess mechanisms to transport sequence nonspecific dsRNA into and between cells.To identify cellular components required for systemic RNAi in C. elegans, we isolated systemic RNAi defective (Sid) mutants defective for spreading of RNAi (7). The first characterized gene, sid-1, encodes a transmembrane protein expressed in all cells sensitive to systemic RNAi and is required for uptake of dsRNA (7, 16). Furthermore, SID-1 expressed in Drosophila S2 cells is sufficient to mediate passive uptake of dsRNA from the growth media, indicating that SID-1 most likely acts as a channel for diffusion of dsRNA into cells (16). These observations provide strong support for the notion that dsRNA is systemically transported in C. elegans.A SID-1::GFP fusion reporter construct that rescues sid-1 mutant worms was expressed at highest levels in cells directly exposed to the environment (7). This observation suggested that environmental dsRNA might enter the animal via these sid-1 expressing cells. Here we describe sid-2, a gene specifically required for uptake of silencing information (hereafter assumed to be dsRNA) from the environment...

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“…Although in vitro feeding assays have been shown to be useful in studying different tick molecules and tick-pathogen interaction [70], its application in RNAi study in ticks has been limited. A study on the Lyme disease vector I. scapularis employed capillary feeding of dsRNA to nymphs to suppress anticomplement gene isac [71]. In another study, adult R.…”

Section: Feedingmentioning

confidence: 99%

“…Other salivary proteins with immunomodulatory function, such as the anti-complement protein, isac [71], and two proteins that can inhibit neutrophil function, ISL 929 and 1373 [85], have also been knockdowned in I. scapularis. Silencing of isac in nymphs, induced by capillary feeding of dsRNA, not only reduced blood feeding, but also decreased the load of the spirochete Borrelia burgdorferi in the tick.…”

Section: Genes Related To Salivary Functionsmentioning

confidence: 99%

RNA Interference – A Powerful Functional Analysis Tool for Studying Tick Biology and its Control

Galay¹,

Umemiya‐Shirafuji²,

MasamiMochizuki³

et al. 2016

RNA Interference

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Ticks (Acari: Ixodida) are blood-sucking arthropods globally recognized as vectors of numerous diseases. They are primarily responsible for the transmission of various pathogens, including viruses, rickettsiae, and blood parasites of animals. Ticks are second to mosquitoes in terms of disease transmission to humans. The continuous emergence of tick-borne diseases and acaricide resistance of ticks necessitates the development of new and more effective control agents and strategies; therefore, understanding of different aspects of tick biology and their interaction with pathogens is very crucial in developing effective control strategies. RNA interference (RNAi) has been widely used in the area of tick research as a versatile reverse genetic tool to elucidate the functions of various tick proteins. During the past decade, numerous studies on ticks utilized RNAi to evaluate potentially key tick proteins involved in blood feeding, reproduction, evasion of host immune response, interaction with pathogens, and pathogen transmission that may be targeted for tick and pathogen control. This chapter reviewed the application of RNAi in tick research over the past decade, focusing on the impact of this technique in the advancement of knowledge on tick and pathogen biology.

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Capillary feeding of specific dsRNA induces silencing of the isac gene in nymphal Ixodes scapularis ticks

Cited by 81 publications

References 62 publications

A Novel Mechanism of Complement Inhibition Unmasked by a Tick Salivary Protein That Binds to Properdin

A Novel Mechanism of Complement Inhibition Unmasked by a Tick Salivary Protein That Binds to Properdin

Caenorhabditis elegans SID-2 is required for environmental RNA interference

RNA Interference – A Powerful Functional Analysis Tool for Studying Tick Biology and its Control

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