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Exploring tick saliva: from biochemistry to ‘sialomes’ and functional genomics

Published online by Cambridge University Press:  19 April 2005

J. G. VALENZUELA
J. G. VALENZUELA
Affiliation:
Vector Molecular Biology Unit, Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, 4 Center Drive, 4/B2-35, Bethesda, MD 20892, USA
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Abstract

Tick saliva, a fluid once believed to be only relevant for lubrication of mouthparts and water balance, is now well known to be a cocktail of potent anti-haemostatic, anti-inflammatory and immunomodulatory molecules that helps these arthropods obtain a blood meal from their vertebrate hosts. The repertoire of pharmacologically active components in this cocktail is impressive as well as the number of targets they specifically affect. These salivary components change the physiology of the host at the bite site and, consequently, some pathogens transmitted by ticks take advantage of this change and become more infective. Tick salivary proteins have therefore become an attractive target to control tick-borne diseases. Recent advances in molecular biology, protein chemistry and computational biology are accelerating the isolation, sequencing and analysis of a large number of transcripts and proteins from the saliva of different ticks. Many of these newly isolated genes code for proteins with homologies to known proteins allowing identification or prediction of their function. However, most of these genes code for proteins with unknown functions therefore opening the road to functional genomic approaches to identify their biological activities and roles in blood feeding and hence, vaccine development to control tick-borne diseases.

Keywords

Functional genomicshigh-throughput approachesmolecular biologypharmacologytick saliva
Type
Research Article
Information
Parasitology , Volume 129 , Issue S1 , October 2004 , pp. S83 - S94
Copyright
© 2004 Cambridge University Press

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References

REFERENCES

ALARCON-CHAIDEZ, F. J., MULLER-DOBLIES, U. U. & WIKEL, S. ( 2003). Characterization of a recombinant immunomodulatory protein from the salivary glands of Dermacentor andersoni. Parasite Immunology 25, 69–77.CrossRefGoogle Scholar
ALJAMALI, M., BOWMAN, A. S., DILLWITH, J. W., TUCKER, J. S., YATES, G. W., ESSENBERG, R. C. & SAUER, J. R. ( 2002). Identity and synthesis of prostaglandins in the lone star tick, Amblyomma americanum (L.), as assessed by radio-immunoassay and gas chromatography/mass spectrometry. Insect Biochemistry and Molecular Biology 32, 331–341.Google Scholar
ALJAMALI, M. N., BIOR, A. D., SAUER, J. R. & ESSENBERG, R. C. ( 2003). RNA interference in ticks: a study using histamine binding protein dsRNA in the female tick Amblyomma americanum. Insect Molecular Biology 12, 299–305.CrossRefGoogle Scholar
ALMAZAN, C., KOCAN, K. M., BERGMAN, D. K., GARCIA-GARCIA, J. C., BLOUIN, E. F. & DE LA FUENTE, J. ( 2003). Identification of protective antigens for the control of Ixodes scapularis infestations using cDNA expression library immunization. Vaccine 21, 1492–1501.CrossRefGoogle Scholar
ANGUITA, J., RAMAMOORTH, N., HOVIUS, J. W. R., DAS, S., THOMAS, V., PERSINSKI, R., CONZE, D., ASKENASE, P. W., RINCON, M., KANTOR, F. S. & FIKRIG, E. ( 2002). Salp15, an Ixodes scapularis salivary protein, inhibits CD4+ T cell activation. Immunity 16, 849–859.CrossRefGoogle Scholar
ANTUCH, W., GUNTERT, P., BILLETER, M., HAWTHORNE, T., GROSSENBACHER, H. & WUTHRICH, K. ( 1994). NMR solution structure of the recombinant tick anticoagulant peptide (rTAP), a FXa inhibitor from the tick Ornithodoros moubata. Federation of Experimental Biology Societies Letters 352, 251–257.CrossRefGoogle Scholar
ARCA, B., LOMBARDO, F., CAPURRO, M., DELLA TORRE, A., SPANOS, L., DIMOPOULOS, G., LOUIS, C., JAMES, A. A. & COLUZZI, M. ( 1999). Salivary gland-specific gene expression in the malaria vector Anopheles gambiae. Parasitologia 41, 483–487.Google Scholar
BELL, J. F., STEWART, S. J. & WIKE, S. K. ( 1979). Resistance to tick-borne Francischella tularensis by tick sensitized rabbits: allergic klendusity. American Journal of Tropical Medicine and Hygiene 28, 876–880.CrossRefGoogle Scholar
BERGMAN, D. K., PALMER, M. J., CAIMANO, M. J., RADOLF, J. D. & WIKEL, S. K. ( 2000). Isolation and molecular cloning of a secreted immunosuppressant protein from Dermacentor andersoni salivary gland. Journal of Parasitology 86, 516–525.CrossRefGoogle Scholar
BINNINGTON, K. C. & KEMP, D. H. ( 1980). Role of tick salivary glands in feeding and disease transmission. Advances in Parasitology 18, 315–339.CrossRefGoogle Scholar
BOWMAN, A. S., GENGLER, C. L., SURDICK, M. R., ZHU, K., ESSENBERG, R. C., SAUER, J. R. & DILLWITH, J. W. ( 1997). A novel phospholipase A2 activity in saliva of the lone star tick, Amblyomma americanum. Experimental Parasitology 87, 121–132.CrossRefGoogle Scholar
BROOKS, D. R. & ISAAC, R. E. ( 2002). Functional genomics of parasitic worms: the dawn of a new era. Parasitology International 51, 319–325.CrossRefGoogle Scholar
BROSSARD, M. ( 1977). Rabbits infested with the adults of Ixodes ricinus L: Passive transfer of resistance with immune serum. Bulletin de la Société de Pathologie Exotique 70, 289–294.Google Scholar
BROSSARD, M., MONNERON, J. P. & PAPATHEODOROU, V. ( 1982). Progressive sensitization of circulating basophils against Ixodes ricinus antigens during repeated infestations of rabbits. Parasite Immunology 4, 335–361.CrossRefGoogle Scholar
BROWN, S. J. & ASKENASE, P. W. ( 1985). Amblyomma americanum: requirement for host Fc receptors in antibody-mediated acquired immune resistance to ticks. Experimental Parasitology 59, 248–256.CrossRefGoogle Scholar
CHAMPAGNE, D. E., SMARTT, C. T., RIBEIRO, J. M. C. & JAMES, A. A. ( 1995). The salivary gland-specific apyrase of the mosquito Aedes aegypti is a member of the 5′-nucleotidase family. Proceedings of the National Academy of Sciences, USA 92, 694–698.CrossRefGoogle Scholar
DAS, S., BENERJEE, G., DEPONTE, K., MARCANTONIO, N., KANTOR, F. S. & FIKRIG, E. ( 2001). Salp25D, an Ixodes scapularis antioxidant, is 1 of 14 immunodominant antigens in engorged tick salivary glands. Journal of Infectious Diseases 184, 1056–1064.CrossRefGoogle Scholar
DICKINSON, R. G., O'HAGAN, J. E., SHOTZ, M., BINNINGTON, K. C. & HEGARTY, M. P. ( 1976). Prostaglandin in the saliva of the cattle tick Boophilus microplus. Australian Journal of Experimental Biology and Medical Science 54, 475–486.CrossRefGoogle Scholar
EDWARDS, J. F., HIGGS, S. & BEATY, B. J. ( 1998). Mosquito feeding-induced enhancement of Cache Valley Virus (Bunyaviridae) infection in mice. Journal of Medical Entomology 35, 261–265.CrossRefGoogle Scholar
EHEBAUER, M. T., MANS, B. J., GASPAR, A. R. M. & NEITZ, A. W. H. ( 2002). Identification of extrinsic blood coagulation pathway inhibitors from the tick Ornithodoros savignyi (Acari: Argasidae). Experimental Parasitology 101, 138–148.CrossRefGoogle Scholar
FERGUSON, J. J. & ZAQQA, M. ( 1999). Platelet glycoprotein IIb/IIIa receptor antagonists: current concepts and future directions. Drugs 58, 965–982.CrossRefGoogle Scholar
FRANCISCHETTI, I. M. B., ANDERSEN, J. F. & RIBEIRO, J. M. C. ( 2002 a). Biochemical and functional characterization of recombinant Rhodnius prolixus platelet aggregation inhibitor 1 a novel lipocalin with high affinity for adenosine diphosphate and other adenine nucleotides. Biochemistry 41, 3810–3818.Google Scholar
FRANCISCHETTI, I. M. B., MATHER, T. N. & RIBEIRO, J. M. C. ( 2003). Cloning of a salivary gland metalloprotease and characterization of gelatinase and fibrin(ogen)lytic activities in the saliva of the Lyme disease tick vector Ixodes scapularis. Biochemical and Biophysical Research Communications 305, 869–875.CrossRefGoogle Scholar
FRANCISCHETTI, I. M. B., VALENZUELA, J. G., ANDERSEN, J. F., MATHER, T. N. & RIBEIRO, J. M. C. ( 2002 b). Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the salivary glands of the tick, Ixodes scapularis: identification of factor X and factor Xa as scaffolds for the inhibition of factor VIIa/tissue factor complex. Blood 99, 3602–3612.Google Scholar
GILLESPIE, R. D., MBOW, M. L. & TITUS, R. G. ( 2000). The immunomodulatory factors of bloodfeeding arthropods saliva. Parasite Immunology 22, 319–331.CrossRefGoogle Scholar
GORDON, J. R. & ALLEN, J. R. ( 1991). Factors V and VII anticoagulant activities in the salivary glands of feeding Dermacentor andersoni ticks. Journal of Parasitology 77, 167–170.CrossRefGoogle Scholar
HAJNICKA, V., FUCHSBERGER, N., SLOVAK, M., KOCAKOVA, P., LABUDA, M. & NUTALL, P. A. ( 1998). Tick salivary gland extracts promote virus growth in vitro. Parasitology 116, 533–538.CrossRefGoogle Scholar
HAJNICKA, V., KOCAKOVA, P., SLAVIKOVA, M., SLOVAK, M., GASPERIK, J., FUCHSBERGER, N. & NUTALL, P. A. ( 2001). Anti-Interleukin-8 activity of tick salivary gland extracts. Parasite Immunology 23, 483–489.CrossRefGoogle Scholar
HAWKINS, R. I. & HELLMANN, K. ( 1966). Factor affecting blood clotting from the tick Ornithodoros moubata. Journal of Physiology 185, 70.Google Scholar
HORN, F., DOS SANTOS, P. C. & TERMIGNONI, C. ( 2000). Boophilus microplus anticoagulant protein: an anti-thrombin inhibitor from the cattle tick saliva. Archives of Biochemistry Biophysics 384, 68–73.CrossRefGoogle Scholar
HUGLI, T. E. & MULLER-EBERHARD, H. J. ( 1978). Anaphylatoxins: C3a and C5a. Advances in Immunology 26, 1–53.CrossRefGoogle Scholar
INOKUMA, H., KEMP, D. H. & WILLADSEN, P. ( 1994). Comparison of Prostaglandin E2 (PGE2) in salivary gland of Boophilus microplus, Haemaphysalis longicornis and Ixodes holocyclus, and quantification of PGE2 in saliva, hemolymph, ovary and gut of B. microplus. Journal of Veterinary and Medical Science 56, 1217–1218.CrossRefGoogle Scholar
IWANAGA, S., OKADA, M., ISAWA, H., MORITA, A. & CHINZEI, Y. ( 2003). Identification and characterization of novel salivary thrombin inhibitors from the ixodidae tick, Haemaphysalis longicornis. European Journal of Biochemistry 270, 1926–1934.CrossRefGoogle Scholar
JOINER, K. A. ( 1988). Complement evasion by bacteria and parasites. Annual Review of Microbiology 42, 201–230.CrossRefGoogle Scholar
JONES, L. D., HODGSON, E. & NUTTALL, P. A. ( 1989). Enhancement of virus transmission by tick salivary glands. Journal of General Virology 70, 1895–1898.CrossRefGoogle Scholar
JONES, L. D. & NUTTALL, P. A. ( 1990). The effect of host resistance to tick infestation on the transmission of Thogoto virus by ticks. Journal of General Virology 71, 1039–1043.CrossRefGoogle Scholar
JOUBERT, A. M., CRAUSE, J. C., GASPAR, A. R., CLARKE, F. C., SPICKETT, M. & NEITZ, A. W. ( 1995). Isolation and characterization of an anticoagulant present in the salivary glands of the bont-legged tick, Hyalomma truncatum. Experimental and Applied Acarology 19, 79–92.CrossRefGoogle Scholar
JOUBERT, A. M., LOUW, A. I., JOUBERT, F. & NEITZ, A. W. H. ( 1998). Cloning, nucleotide sequence and expression of the gene encoding FXa inhibitor from the salivary glands of the tick Ornithodoros savigny. Experimental and Applied Acarology 22, 603–619.CrossRefGoogle Scholar
JUTEL, M., WATANABE, T., KLUNKER, S., AKDIS, M., THOMET, O. A., MALOLEPSZY, J., ZAK-NEJMARK, T., KOGA, R., KOBAYASHI, T., BLASER, K. & AKDIS, C. A. ( 2001). Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature 413, 420–425.CrossRefGoogle Scholar
KARCZEWSKI, J., ENDRIS, R. & CONNOLLY, T. M. ( 1994). Disagregin is a fibrinogen receptor antagonist lacking the Arg-Gly-Asp sequence from the tick, Ornithodoros moubata. Journal of Biological Chemistry 269, 6702–6708.Google Scholar
KARCZEWSKI, J., WAXMAN, L., ENDRIS, R. G. & CONNOLLY, T. M. ( 1995). An inhibitor from the argasid tick Ornithodoros moubata of cell adhesion to collagen. Biochemical and Biophysical Research Communications 208, 532–541.CrossRefGoogle Scholar
KELLER, P. M., WAXMAN, L., ARNOLD, B. A., SCHULTZ, L. D., CONDRA, C. & CONNOLLY, T. M. ( 1993). Cloning of the cDNA and expression of moubatin, an inhibitor of platelet aggregation. Journal of Biological Chemistry 268, 5450–5456.Google Scholar
KROCOVA, Z., MACELA, A., HERNYCHOVA, L., KROCA, M., PECHOVA, J. & KOPECKY, J. ( 2003). Tick salivary gland extract accelerates proliferation of Franciscella tularensis in the host. Journal of Parasitology 89, 14–20.CrossRefGoogle Scholar
LABUDA, M., JONES, L. D., WILLIAMS, T. & NUTTALL, P. A. ( 1993). Enhancement of tick-borne encephalitis virus transmission by tick salivary gland extract. Medical Veterinary Entomology 7, 193–196.CrossRefGoogle Scholar
LEBOULLE, G., CRIPPA, M., DECREM, Y., MEJRI, N., BROSSARD, M., BOLLEN, A. & GODFROID, E. ( 2002 a). Characterization of a novel salivary immunosuppressive protein from Ixodes ricinus ticks. Journal of Biological Chemistry 277, 10083–10089.Google Scholar
LEBOULLE, G., ROCHEZ, C., LOUAHED, J., RUTTI, B., BROSSARD, M., BOLLEN, A. & GODFROID, E. ( 2002 b). Isolation of Ixodes ricinus salivary gland mRNA encoding factors induced during blood feeding. American Journal of Tropical Medicine and Hygiene 66, 225–233.Google Scholar
LIMESAND, K. H., HIGGS, S., PEARSON, L. D. & BEATY, B. J. ( 2000). Potentiation of vesicular stomatitis New Jersey virus infection in mice by mosquito saliva. Parasite Immunology 22, 461–467.CrossRefGoogle Scholar
LIMO, M. K., VOIGT, W. P., TUMBO-OERI, A. G., NJOGI, R. M. & OLE-MOI, O. K. ( 1991). Purification and characterization of an anticoagulant from the salivary glands of the ixodid tick, Rhipicephalus appendiculatus. Experimental Parasitology 72, 418–429.CrossRefGoogle Scholar
MANS, B. J., COETZEE, J., LOUW, A. I., GASPAR, A. R. M. & NEITZ, A. W. H. ( 2000). Disaggregation of aggregated platelets by apyrase from the tick, Ornithodoros savignyi (Acari: Argasidae). Experimental and Applied Acarology 24, 271–282.CrossRefGoogle Scholar
MANS, B. J., LOUW, A. I. & NEITZ, A. W. H. ( 2002 a). Savignygrin, a platelet aggregation inhibitor from the soft tick Ornithodoros savignyi, presents the RGD integrin recognition motif on the kunitz-BPTI fold. Journal of Biological Chemistry 277, 21371–21378.Google Scholar
MANS, B. J., LOUW, A. I. & NEITZ, A. W. H. ( 2002 b). Amino acid sequence and structure modeling of savignin, a thrombin inhibitor from the tick, Ornithodoros savignyi. Insect Biochemistry and Molecular Biology 32, 821–828.Google Scholar
MANS, B. J., LOUW, A. I. & NEITZ, A. W. H. ( 2002 c). Evolution of hematophagy in ticks: common origins for blood coagulation and platelet aggregation inhibitors from soft ticks of the genus Ornithodoros. Molecular Biology and Evolution 19, 1695–1705.Google Scholar
MANS, B. J., LOUW, A. I. & NEITZ, A. W. ( 2003). The major tick salivary gland proteins and toxins from the soft tick, Ornithodoros savignyi are part of the tick lipocalin family: implications for the origins of tick toxicoses. Molecular Biology and Evolution 20, 1158–1167.CrossRefGoogle Scholar
NARASIMHAN, S., KOSKI, R. A., BEAULIEU, B., ANDERSON, J. F., RAMAMOORTHI, N., KANTOR, F., CAPPELLO, M. & FIKRIG, E. ( 2002). A novel family of anticoagulants from the saliva of Ixodes scapularis. Insect Molecular Biology 11, 641–650.CrossRefGoogle Scholar
NAZARIO, S., DAS, S., DE SILVA, A. M., DEPONTE, K., MARCANTONIO, N., ANDERSON, J. F., FISH, D., FIKRIG, E. & KANTOR, F. S. ( 1998). Prevention of Borrelia burgdorferi transmission in guinea pig by tick immunity. American Journal of Tropical Medicine and Hygiene 58, 780–785.CrossRefGoogle Scholar
NENE, V., LEE, D., QUACKENBUSH, J., SKILTON, R., MWAURA, S., GARDNER, M. J. & BISHOP, R. ( 2002). AvGI, an index of genes transcribed in the salivary glands of the ixodid tick Amblyomma variegatum. International Journal of Parasitology 32, 1447–1456.CrossRefGoogle Scholar
NIENABER, J., GASPAR, A. R. M. & NEITZ, A. W. H. ( 1999). Savignin, a potent thrombin inhibitor isolated from the salivary glands of the tick, Ornithodoros savignyi (Acari: Argasidae). Experimental Parasitology 93, 82–91.CrossRefGoogle Scholar
PAESEN, G. C., ADAMS, P. L., HARLOS, K., NUTTALL, P. A. & STUART, D. I. ( 1999). Tick histamine-binding proteins: isolation, cloning and three dimensional structure. Molecular Cell 3, 661–671.CrossRefGoogle Scholar
PECHOVA, J., STEPANOVA, G., KOVAR, L. & KOPECKY, J. ( 2002). Tick salivary gland extract-activated transmission of Borrelia afzelii spirochaetes. Folia Parasitol (Praha) 49, 153–159.CrossRefGoogle Scholar
QUACKENBUSH, J., CHO, J., LEE, D., LIANG, F., HOLT, I., KARAMYCHEVA, S., PARVIZI, B., PERTEA, G., SULTANA, R. & WHITE, J. ( 2001). The TIGR gene indices: analysis of gene transcript sequences in highly sampled eukaryotic species. Nucleic Acids Research 29, 159–164.CrossRefGoogle Scholar
RIBEIRO, J. M. C. ( 1987 a). Role of saliva in blood-feeding by arthropods. Annual Review of Entomology 32, 463–478.Google Scholar
RIBEIRO, J. M. C. ( 1987 b). Ixodes dammini: salivary anti-complement activity. Experimental Parasitology 64, 347–353.Google Scholar
RIBEIRO, J. M. C. ( 1989). Role of saliva in tick/host interactions. Experimental and Applied Acarology 7, 15–20.CrossRefGoogle Scholar
RIBEIRO, J. M. C. ( 1995). Blood-feeding arthropods: live syringes or invertebrate pharmacologists? Infectious Agents of Disease 4, 143–152.Google Scholar
RIBEIRO, J. M. C., ENDRIS, T. M. & ENDRIS, R. ( 1991). Saliva of the soft tick, Ornithodoros moubata, contains anti-platelet and apyrase activities. Comparative Biochemistry and Physiology Part A 100, 109–112.CrossRefGoogle Scholar
RIBEIRO, J. M. C., EVANS, P. M., MACSWAIN, J. L. & SAUER, J. ( 1992). Amblyomma americanum: characterization of salivary prostaglandins E2 and F2α by RP-HPLC/bioassay and gas chromatography-mass spectrometry. Experimental Parasitology 74, 112–116.CrossRefGoogle Scholar
RIBEIRO, J. M. C., MAKOUL, G., LEVINE, J., ROBINSON, D. & SPIELMAN, A. ( 1985). Antihemostatic, anti-inflammatory and immunosuppressive properties of the saliva of the tick, Ixodes dammini. Journal of Experimental Medicine 161, 332–344.CrossRefGoogle Scholar
RIBEIRO, J. M. C., MAKOUL, G. T. & ROBINSON, D. R. ( 1988). Ixodes dammini: evidence for salivary prostacyclin secretion. Journal of Parasitology 74, 1068–1069.CrossRefGoogle Scholar
RIBEIRO, J. M. C. & MATHER, T. N. ( 1998). Ixodes scapularis: salivary kininase activity is a metallo dipetidyl carboxypeptidase. Experimental Parasitology 89, 213–221.CrossRefGoogle Scholar
RIBEIRO, J. M. C., WEIS, J. J. & TELFORD III, S. R. ( 1990). Saliva of the tick Ixodes dammini inhibits neutrophil function. Experimental Parasitology 70, 382–388.CrossRefGoogle Scholar
SANGAMNATDEJ, S., PAESEN, G. C., SLOVAK, M. & NUTALL, P. A. ( 2002). A high affinity serotonin- and histamine-binding lipocalin from tick saliva. Insect Molecular Biology 11, 79–86.CrossRefGoogle Scholar
SHAW, M. K., TILNEY, L. G. & McKEEVER, D. J. ( 1993). Tick salivary gland extract and interleukin-2 stimulation enhance susceptibility of lymphocyte to infection by Theileria parva sporozoites. Infection and Immunity 61, 1486–1495.Google Scholar
ST CHARLES, R., PADMANABHAN, K., ARNI, R. V., PADMANABHAN, K. P. & TULINSKY, A. ( 2000). Structure of tick anticoagulant peptide at 1·6 A resolution complexed with bovine pancreatic trypsin inhibitor. Protein Science 9, 265–272.CrossRefGoogle Scholar
TITUS, R. G. & RIBEIRO, J. M. C. ( 1988). Salivary gland lysates from the sand fly Lutzomyia longipalpis enhance Leishmania infectivity. Science 239, 1306–1308.CrossRefGoogle Scholar
TRAGER, W. ( 1939). Acquired immunity to ticks. Journal of Parasitology 25, 57–78.CrossRefGoogle Scholar
VALENZUELA, J. G. ( 2002). High-throughput approaches to study salivary proteins and genes from vectors of disease. Insect Biochemistry and Molecular Biology 32, 1199–1209.CrossRefGoogle Scholar
VALENZUELA, J. G., BELKAID, Y., GARFIELD, M. K., MENDEZ, S., KAMHAWI, S., ROWTON, E., SACKS, D. L. & RIBEIRO, J. M. C. ( 2001 b). Toward a defined anti-Leishmania vaccine targeting vector antigens: characterization of a protective salivary protein. Journal of Experimental Medicine 194, 331–345.Google Scholar
VALENZUELA, J. G., BELKAID, Y., ROWTON, E. & RIBEIRO, J. M. C. ( 2001 a). The salivary apyrase of the blood-sucking sand fly Phlebotomus papatasi belongs to the novel Cimex family of apyrases. Journal of Experimental Biology 204, 229–237.Google Scholar
VALENZUELA, J. G., CHARLAB, R., GALPERIN, M. Y. & RIBEIRO, J. M. C. ( 1998). Purification, cloning and expression of an apyrase from the bed bug Cimex lectularius. A new type of nucleotide-binding enzyme. Journal of Biological Chemistry 273, 30583–30590.Google Scholar
VALENZUELA, J. G., CHARLAB, R., MATHER, T. N. & RIBEIRO, J. M. C. ( 2000). Purification, cloning and expression of a novel salivary anti-complement protein from the tick, Ixodes scapularis. Journal of Biological Chemistry 275, 18717–18723.CrossRefGoogle Scholar
VALENZUELA, J. G., FRANCISCHETTI, I. M. B., PHAM, V. M., GARFIELD, M. K., MATHER, T. N. & RIBEIRO, J. M. C. ( 2002). Exploring the sialome of the tick Ixodes scapularis. Journal of Experimental Biology 205, 2843–2864.Google Scholar
VAN DE LOCHT, A., STUBBS, M. T., BODE, W., FRIEDRICH, T., BOLLSCHWEILER, C., HOFFKEN, W. & HUBER, R. ( 1996). The ornithodorin-thrombin crystal structure, a key to the TAP enigma? EMBO Journal 15, 6011–6017.Google Scholar
WANG, X., COONS, L. B., TAYLOR, D. B., STEVENS, S. E. Jr. & GARTNER, T. K. ( 1996). Variabilin, a novel RGD-containing antagonist of glycoprotein IIb-IIIa and platelet aggregation inhibitor from the hard tick Dermacentor variabilis. Journal of Biological Chemistry 271, 17785–17790.CrossRefGoogle Scholar
WAXMAN, L., SMITH, D. E., ARCURI, K. E. & VLASUK, G. P. ( 1990). Tick anticoagulant peptide is a novel inhibitor of blood coagulation factor Xa. Science 248, 593–596.CrossRefGoogle Scholar
WHITTON, J. L., RODRIGUEZ, F., ZHANG, J. & HASSET, D. E. ( 1999). DNA immunization: mechanistic studies. Vaccine 17, 1612–1619.CrossRefGoogle Scholar
WIKEL, S. K. ( 1996). Host immunity to ticks. Annual Review of Entomology 41, 1–22.CrossRefGoogle Scholar
WIKEL, S. K. ( 1999). Tick modulation of host immunity: an important factor in pathogen transmission. International Journal of Parasitology 28, 851–859.CrossRefGoogle Scholar
WIKEL, S. K. & ALLEN, J. R. ( 1976). Acquired resistance to ticks. Passive transfer of resistance. Immunology 30, 311–316.Google Scholar
WIKEL, S. K., RAMACHANDRA, R. N., BERGMAN, D. K., BURKOT, T. R. & PIESMAN, J. ( 1997). Infestation with pathogen-free nymphs of the tick Ixodes scapularis induces host resistance to transmission of Borrelia burgdorferi by ticks. Infection and Immunity 65, 335–338.Google Scholar
ZHU, K., BOWMAN, A. S., BRIGHAM, D. L., ESSENBERG, R. C., DILLWITH, J. W. & SAUER, J. R. ( 1997 a). Isolation and characterization of americanin, a specific inhibitor of thrombin, from the salivary glands of the lone star tick Amblyomma americanum (L.). Experimental Parasitology 87, 30–38.Google Scholar
ZHU, K., DILLWITH, J. W., BOWMAN, A. S. & SAUER, J. R. ( 1997 c). Identification of hemolytic activity in saliva of the lone star tick (Acari: Ixodidae). Journal of Medical Entomology 34, 160–166.Google Scholar
ZHU, K., SAUER, J. R., BOWMAN, A. S. & DILLWITH, J. W. ( 1997 b). Identification and characterization of anticoagulant activities in the saliva of the lone star tick, Amblyomma americanum (L). Journal of Parasitology 83, 38–43.Google Scholar