Identifier

etd-11142014-233558

Degree

Doctor of Philosophy (PhD)

Department

Veterinary Medical Sciences - Pathobiological Sciences

Document Type

Dissertation

Abstract

Dengue virus (DENV) is maintained in a primarily anthroponotic cycle between humans and the mosquito, Aedes aegypti. Investigations into DENV infection of the vertebrate host generally do not account for the contribution of vector saliva, an inherent part of the mosquito-borne viral inoculum. Feeding by mosquitoes on vertebrate hosts is initiated by probing, which results in physical damage to the skin and vasculature, and the simultaneous introduction of DENV and saliva into the skin. Saliva contains many individual proteins with the potential to modulate host hemostasis and immune responses, thereby facilitating blood feeding and virus transmission. As exogenous antigens, both DENV and these salivary proteins encounter the vertebrate host immune system and consequently could have an effect on the immunological environment and response of the bite site during viral establishment, as well as the ensuing viremia. My overarching hypothesis is that mosquito saliva aids in the establishment of DENV infections within the vertebrate, and that distinct immunological alterations involved in this enhancement will be attributable to individual salivary proteins. I therefore conducted investigations into the triad of vector-virus-vertebrate interactions aimed at further characterizing 1) the strain-based impact of DENV infection on salivary protein transcript expression in Ae. aegypti; 2) the probing-based modulation of vertebrate immune responses during DENV infection in the skin of a murine model of transmission; 3) the effect of individual salivary proteins on DENV production in a human hematopoietic cell line; and 4) the influence of the salivary protein ‘aegyptin’ on DENV infection in the mouse; with emphasis on early, establishment-relevant time points and differences in infection kinetics with the potential to alter transmission success.

Date

2014

Document Availability at the Time of Submission

Student has submitted appropriate documentation to restrict access to LSU for 365 days after which the document will be released for worldwide access.

Committee Chair

Mores, Christopher

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