Bloodmeal determinants of Zika virus infection of Aedes (Stegomyia) aegypti mosquitoes



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The following dissertation aims to ascertain how factors in the blood of viremic mammals influence the infection of Aedes (Stegomyia) spp. mosquitoes with the arboviruses Zika (ZIKV). It has been repeatedly observed in both flaviviruses and alphaviruses that bloodmeals taken from viremic animals are more infectious than artificial bloodmeals. Although this finding has been demonstrated to be at least in part mediated by clotting factors facilitating increased viral contact with the mosquito midgut epithelium following a natural bloodmeal, a comprehensive and mechanistic exploration of this observation has not been undertaken, a gap the proposed project seeks to address. I hypothesize that there are endocrine, inflammatory, and chemical factors of in vivo mammalian blood, resulting from viral infection, that increase the oral infection by ZIKV in Aedes aegypti mosquitoes. Utilizing multiple mosquito species (Aedes aegypti, Ae. albopictus, Culex quinquefasciatus, and Sabethes cyaneus) I first determined the general basal levels of vector competence these species demonstrated for various strains of ZIKV. Subsequently experiments directly comparing artificial bloodmeals derived from murine and non-human primates to ZIKV viremic animals were conducted to ascertain what, if any, soluble factors were found in association with any instances of increased infectivity in Ae. aegypti. Finally, manipulation of the constituents of bloodmeals were conducted by means of artificial supplementation of bloodmeals (glycation of erythrocytes, addition of TGF-β) as well as via utilization of genetically modified mice (LEPRdb/db; displaying a type II diabetic/metabolic syndrome-like phenotype). Corresponding to previous reports, I found that viremic animals largely proved more infectious than artificial bloodmeals, although in some experimental paradigms (NHPs) this was not found to be statistically significant. Strikingly, in murine bloodmeals the use of “semi-artificial” bloodmeals (whole blood mixed 1:1 with virus) as opposed to washed erythrocytes mixed with virus increased infectivity of ZIKV in Ae. aegypti mosquitoes. Furthermore, artificially glycated erythrocytes, or inclusion of TGF-β in bloodmeals substantially increased infectivity of ZIKV in Ae. aegypti suggesting that elements of blood lost in some artificial bloodmeal formulations may play a role in the observed loss of infectivity. These findings are incorporated into recommendations for vector competence study designs settings of both high and low resources.



Biology, Virology, Biology, Entomology, Biology, Microbiology