(500-7900 characters long) Vector arthropods, such as mosquitoes, triatomine bugs and ticks, salivate while they puncture our skin in their search of blood. This saliva contains dozens to hundreds of compounds that have anti-clotting, anti-platelet, vasodilatory, anti-inflammatory, and immunomodullatory functions. While helping the vector to feed, it also modifies the site where pathogens are injected and in many cases facilitates the infection process. For this reason, salivary proteins of vectors can be used as vaccine targets for the diseases they transmit. Salivary proteins can also be used as immuno-epidemiological markers of vector exposure, and in themselves can have potent and novel pharmacological activities. Because the saliva of hematophagous animals is under attack of their host's immune system, their constituents are under a rapid evolutionary pressure in an arms'race scenario with their hosts, causing an enormous variety of unique protein families even in closely related organisms. The section of vector biology aims at uncovering the biodiversity of salivary proteins in the near 500 genera of blood sucking arthropods, and to discover the function of the novel protein families that we encounter. Accordingly we have developed a two pronged approach focusing in sialotranscriptome discovery projects and functional sialomic studies. In addition to these core studies on the saliva of vector arthropods, the section also collaborates with Drs. Robert Gwadz and Tovi Lehmann in the ecology of Anopheles gambiae, and has also collaborated with other members of the LMVR and other extramural scientists lending its expertise in bioinformatics, structural biology and vascular biology. Sialotranscriptome discovery projects: Because host hemostasis (the physiological process that prevents blood loss, consisting of platelet aggregation, blood clotting and vasoconstriction) is a complex and redundant phenomenon, the salivary glands of blood sucking arthropods consist of a magic potion with diverse chemicals that in a redundant way counteract host mechanisms to prevent blood loss, allowing the fast acquisition of a meal. Salivary transcriptome made in the past few years indicate that the magic potion consists of 70-100 different proteins in the case of mosquitoes, for example, to over 1,000 in the case of ticks (Ticks feed for several days and have to disarm host immune reactions, in addition to the hemostatic system). Transcriptome studies also show that the salivary proteins of blood sucking arthropods are at a very fast pace of evolution, perhaps explaining why every genera studied so far has several unique protein families. Indeed there are unique proteins found at the subgenus level. Given we can now describe in detail the sialotranscriptome (from the Greek word sialo = saliva) of a single organism, we can ask now what is the universe of salivary proteins associated to blood feeding, the so called sialoverse. There are near 19,000 species of blood sucking arthropods in 500 different genera. If we find (minimally) 5 novel protein families per genus (within the 70-500 proteins in each sialome), there are at least 2,500 novel proteins to be discovered, each one with an interesting pharmacological property. We have so far explored less than 20 genera of blood sucking arthropods, and it is our goal to extend sialotranscriptome discovery to map this pharmacological mine for future studies, and in the process learn the paths taken by genomes in their evolution to blood feeding, and identify proteins with pharmacological and vaccine potential. In the current fiscal year (2012), members of the Section of Vector Biology contributed to a total of 22 papers and 3 reviews. Seven papers relate to sialotranscriptome discovery, including two triatomine bugs, the South American Triatoma matogrossensis, associated with Chagas'disease transmission and possible inducer of pemphigus foliaceus, and Triatoma rubida, the most important triatomine causing allergies in Arizona (1-2). Three sialotranscriptomes of ticks were published, that for the Gulf Coast tick Amblyomma maculatum (3), for Hyalomma marginatum (the first for this genus) (4) and for Antricola delacruzi (5), of interest for the evolution of blood feeding in ticks. The sialotranscriptome of the river blindness vector in South America, Simulium guianense, was also disclosed (6). Novel protein families were discovered in the majority of these studies. A microarray probing the salivary mRNA expression of Ixodes scapularis following infection with virus was also produced (7). Functional sialomic studies: We advanced our knowledge regarding the function of several salivary proteins, as well as discovering novel salivary properties, as reported in 8 publications. Two publications describe the structure and function of salivary proteins with anti-platelet and vasodilatory properties (8-9), one of which (9) is a candidate vaccine against Leishmaniasis. Two proteins with anti-clotting activity were described (10-11), one of which has anti-inflammatory and anti-thrombotic activity in vivo (10). A triatomine protein (Triplatin), with anti-platelet activity was functionally characterized as a scavenger of thromboxane A2 (12). Adenosine and the protein LJM 111 from sand flies were implicated as having anti-inflammatory activities in in vivo models of inflammation (13-14). Ixolaris, an anti-tissue factor/FXA inhibitor from ticks was shown to inhibit tumor growth and metastasis in a murine model (15), and the tick-derived sialostatin L was shown to be an effective inhibitor of experimental asthma (16). Review articles: Members of the section participated in writing 3 review articles on the subject of salivary components of blood sucking arthropods (17-19) Bioinformatic collaborations: Dr. Ribeiro collaborated with Dr. Struchiner (Fiocruz Brazil) and Dr. Nutman (LPD) on transposable elements of Anopheles gambiae (20) and the identification of allergens of human importance (21) Other collaborations: Dr Francischetti helped Drs. S. Pierce and L. Miller laboratory on the identification of an anti-inflammatory protein of Plasmodium falciparum (22), and Dr. Ribeiro collaborated with Drs. Gwadz and Lehmann section on the dynamics of Anopheles gambiae swarms (23-25).

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Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2012
Total Cost
$1,187,399
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Ferreira, Viviana P; Fazito Vale, Vladimir; Pangburn, Michael K et al. (2016) SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis. Sci Rep 6:19300
Perner, Jan; Provazník, Jan; Schrenková, Jana et al. (2016) RNA-seq analyses of the midgut from blood- and serum-fed Ixodes ricinus ticks. Sci Rep 6:36695
Gulia-Nuss, Monika; Nuss, Andrew B; Meyer, Jason M et al. (2016) Genomic insights into the Ixodes scapularis tick vector of Lyme disease. Nat Commun 7:10507
Benoit, Joshua B; Adelman, Zach N; Reinhardt, Klaus et al. (2016) Unique features of a global human ectoparasite identified through sequencing of the bed bug genome. Nat Commun 7:10165
Santiago, Paula Beatriz; Assumpção, Teresa C F; de Araújo, Carla Nunes et al. (2016) A Deep Insight into the Sialome of Rhodnius neglectus, a Vector of Chagas Disease. PLoS Negl Trop Dis 10:e0004581
Fernández-Medina, R D; Granzotto, A; Ribeiro, J M et al. (2016) Transposition burst of mariner-like elements in the sequenced genome of Rhodnius prolixus. Insect Biochem Mol Biol 69:14-24
Mendes-Sousa, Antonio F; Queiroz, Daniel C; Vale, Vladimir F et al. (2016) An Inhibitor of the Alternative Pathway of Complement in Saliva of New World Anopheline Mosquitoes. J Immunol 197:599-610
Abdeladhim, Maha; V Coutinho-Abreu, Iliano; Townsend, Shannon et al. (2016) Molecular Diversity between Salivary Proteins from New World and Old World Sand Flies with Emphasis on Bichromomyia olmeca, the Sand Fly Vector of Leishmania mexicana in Mesoamerica. PLoS Negl Trop Dis 10:e0004771
Ribeiro, José M C; Martin-Martin, Ines; Arcà, Bruno et al. (2016) A Deep Insight into the Sialome of Male and Female Aedes aegypti Mosquitoes. PLoS One 11:e0151400
Assumpção, Teresa C; Ma, Dongying; Mizurini, Daniella M et al. (2016) In Vitro Mode of Action and Anti-thrombotic Activity of Boophilin, a Multifunctional Kunitz Protease Inhibitor from the Midgut of a Tick Vector of Babesiosis, Rhipicephalus microplus. PLoS Negl Trop Dis 10:e0004298

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