Isolation and characterization of two novel serpins from the tick Rhipicephalus haemaphysaloides

Yon, YU; Cao, Jie; Zhou, Yongzhi; Zhang, Houshuang; Zhou, Jinlin

doi:10.1016/j.ttbdis.2013.02.001

Cited by 39 publications

(41 citation statements)

References 31 publications

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“…In this study, serpins were also identified in the viscera transcriptome which would also be associated with the digestion of host blood proteins. Serpins have been reported in I. ricinus (Iris) (Prevot et al, 2009), A. americanum (Mulenga et al, 2013), Haemaphysalis longicornis (Imamura et al, 2005), Rhipicephalus haemaphysaloides (Yu et al, 2013) and R. microplus (Rodriguez Valle et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome and toxin family analysis of the paralysis tick, Ixodes holocyclus

Rodriguez-Valle

Moolhuijzen

Barrero

et al. 2018

International Journal for Parasitology

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The Australian paralysis tick (Ixodes holocyclus) secretes neuropathic toxins into saliva that induce host paralysis. Salivary glands and viscera were dissected from fully engorged female I. holocyclus ticks collected from dogs and cats with paralysis symptoms. cDNA from both tissue samples were sequenced using Illumina HiSeq 100 bp pair end read technologies. Unique and nonredundant holocyclotoxin (HT) sequences were designated as HT2 to HT19, as none were identical to the previously described HT1. Specific binding to rat synaptosomes was determined for synthetic HTs, and their neurotoxic capacity was determined by neonatal mouse assay. They induced a powerful paralysis in neonatal mice, particularly HT4 which produced rapid and strong respiratory distress in all animals tested. This is the first known genomic database developed for the Australian paralysis tick. The database contributed to the identification and subsequent characterization of the holocyclotoxin family that will inform the development of novel anti-paralysis control methods.

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Section: Discussionmentioning

confidence: 99%

Transcriptome and toxin family analysis of the paralysis tick, Ixodes holocyclus

Rodriguez-Valle

Moolhuijzen

Barrero

et al. 2018

International Journal for Parasitology

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“…From this perspective, it is proposed that ticks inject serpins into the host to mediate evasion of host defenses and thus they could be suitable targets for tick vaccines (Mulenga et al, 2001). Several tick serpin-encoding cDNAs have been cloned and characterized, including serpins of A. americanum (Mulenga et al, 2007; Porter et al, 2015), Amblyomma maculatum (Karim et al, 2011), Ixodes scapularis (Ribeiro et al, 2006; Mulenga et al, 2009), Ixodes ricinus (Leboulle et al, 2002; Prevot et al, 2006; Chmelar et al, 2011) , Rhipicephalus microplus (Rodriguez-Valle et al, 2012; Tirloni et al, 2014b), Rhipicephalus appendiculatus (Mulenga et al, 2003a), Rhipicephalus haemaphysaloides (Yu et al, 2013), and Haemaphysalis longicornis (Sugino et al, 2003; Imamura et al, 2005, 2006). As of January 2015, more than 200 tick serpin-encoding cDNAs were available in public databases (Porter et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, the presence of serpins in tick saliva was well demonstrated though saliva proteomic studies in Dermacentor andersoni (Mudenda et al, 2014) and R. microplus (Tirloni et al, 2014a) as well as being inferred from transcriptional analysis of salivary glands from A. americanum (Mulenga et al, 2007; Porter et al, 2015), A. maculatum (Karim et al, 2011), Amblyomma triste , Amblyomma parvum , Amblyomma cajennense (Garcia et al, 2014), Amblyomma variegatum (Ribeiro et al, 2011), Hyalomma marginatum rufipes (Francischetti et al, 2011), I. scapularis (Valenzuela et al, 2002; Ribeiro et al, 2006; Mulenga et al, 2009), I. ricinus (Leboulle et al, 2002; Schwarz et al, 2013, 2014), R. appendiculatus (Mulenga et al, 2003a, b), R. microplus (Tirloni et al, 2014b), R. haemaphysaloides (Yu et al, 2013), H. longicornis (Sugino et al, 2003; Imamura et al, 2005), and Antricola delacruzi (Ribeiro et al, 2012). Accordingly, inhibitory tick serpins have been found and characterized in tick saliva, including A. americanum salivary serpin (AAS) 6 (Mulenga et al, 2007; Chalaire et al, 2011), a cross-class inhibitor of papain and trypsin-like proteases able to inhibit blood clotting and complement activation (Mulenga et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, I. ricinus serpin Iris2 inhibited inflammation by inhibiting cathepsin G and chymase (Chmelar et al, 2011). Rhipicephalus haemaphysaloides has two serpins which are able to inhibit chymotrypsin (Yu et al, 2013). In another study, Rodriguez-Valle et al (2012) reported a characterization of R. microplus serpin-3, an inhibitor of trypsin and thrombin that is recognized by naturally tick-infested bovine serum, and antibodies against an epitope of this protein impairs tick fertility.…”

Section: Introductionmentioning

confidence: 99%

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Conserved Amblyomma americanum tick Serpin19, an inhibitor of blood clotting factors Xa and XIa, trypsin and plasmin, has anti-haemostatic functions

Kim

Tirloni

Radulović

et al. 2015

International Journal for Parasitology

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Tick saliva serine protease inhibitors (serpins) facilitate tick blood meal feeding through inhibition of protease mediators of host defense pathways. We previously identified a highly conserved Amblyomma americanum serpin (AAS) 19 that is characterized by its reactive center loop being 100% conserved in ixodid ticks. In this study, biochemical characterization reveals that the ubiquitously transcribed AAS19 is an anti-coagulant protein, inhibiting the activity of five of the eight serine protease blood clotting factors. Pichia pastoris-expressed recombinant (r) AAS19 inhibits the enzyme activity of trypsin, plasmin and blood clotting factors (f) Xa and XIa, with stoichiometry of inhibition estimated at 5.1, 9.4, 23.8 and 28, respectively. Similar to typical inhibitory serpins, rAAS19 forms irreversible complexes with trypsin, fXa and fXIa. At a higher molar excess of rAAS19, fXIIa is inhibited by 82.5%, and thrombin (fIIa), fIXa, chymotrypsin and tryptase are inhibited moderately by 14 – 29%. In anti-hemostatic functional assays, rAAS19 inhibits thrombin but not ADP and cathepsin G activated platelet aggregation, delays clotting in recalcification and thrombin time assays by up to 250 s, and up to 40 s in the activated partial thromboplastin time assay. Given AAS19 high cross-tick species conservation, and specific reactivity of rAAS19 with antibodies to A. americanum tick saliva proteins, we conclude that rAAS19 is a potential candidate for development of a universal tick vaccine.

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“…The attachment site of longistatin-silenced H. longicornis ticks did not show pathological changes, such as hemorrhagic lesions corresponding to the blood pool, while the attachment site of ticks simultaneously silenced acidic chitinases exhibited blood leakage and these ticks can be easily removed. Various protease inhibitors that have roles in anti-hemostatic, anti-inflammatory, and immunomodulatory mechanism have been also characterized using RNAi, including a cystatin, sialostatine L [81], a Kunitz type protease inhibitor, rhipilin [82], and serine protease inhibitors (serpin) [83,84].…”

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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Isolation and characterization of two novel serpins from the tick Rhipicephalus haemaphysaloides

Cited by 39 publications

References 31 publications

Transcriptome and toxin family analysis of the paralysis tick, Ixodes holocyclus

Transcriptome and toxin family analysis of the paralysis tick, Ixodes holocyclus

Conserved Amblyomma americanum tick Serpin19, an inhibitor of blood clotting factors Xa and XIa, trypsin and plasmin, has anti-haemostatic functions

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

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