Date of Award

Winter 2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

Committee Director

Hameeda Sultana

Committee Member

Girish Neelakanta

Committee Member

Emilia Oleszak

Committee Member

Stephen Beebe

Abstract

Vector-borne diseases (VBDs) require urgent attention as they have a high mortality rate, with 700,000 people dying in a year as of 2017. So far, extremely few reliable vaccination strategies and solutions have emerged. Transmission blocking vaccines are one among many solutions available to manage the control of VBDs. These require identification of both vector and pathogen molecules that play important roles in the transmission, dissemination and establishment of VBDs. Our strategy is to characterize these candidates that play important roles in vector-host-pathogen interactions. This manuscript presents two such studies identifying the participation of two arthropod molecules in vector-host-pathogen interactions. The first study uses quantitative and standard PCR to detect dengue serotypes DENV2/3 RNA and immunoblotting to detect viral proteins within mosquito extracellular vesicles (EVs). The EVs carry infectious viral RNA and are able to establish infection in naïve, recipient cells of various lineages. Mosquito EVs mediate DENV2 transmission through a newly identified mosquito exosome marker, designated as Tsp29Fb, an orthologue of human CD63. Silencing Tsp29Fb reduced DENV2 load, it’s interaction with DENV2 E-protein and transmission of DENV2 through EVs.

Our second study identifies another arthropod molecule in ticks. The tick HSP70-like molecule is involved in disrupting the host coagulation pathway through the induction of fibrinogenolysis. Immunoblotting analysis revealed reduced D-Dimer, a fibrin degradation product, in ticks fed on immunocompromised hosts. In addition, ticks fed on immunocompromised hosts exhibit a lower expression of the arthropod HSP70-like molecule that correlated with higher engorgement weights. This differential activity is linked to the immune states and/or background of the vertebrate host, in this case mice. Inhibition of the tick HSP70-like molecule in the salivary gland lysates of fed ticks abrogates its fibrinogenolytic activity. These studies together identify two strong candidates playing different roles for blocking the transmission of VBDs from two different arthropods.

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DOI

10.25777/qa8c-kk58

ISBN

9780438900257

ORCID

0000-0002-5693-5783

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