Date of Award

1-1-2024

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Biomedical Sciences

Dissertation/Thesis Chair

Alexander T Ciota

Committee Members

Gregory Ebel, Jan Conn, Kathleen McDonough, Linda Styer

Keywords

Mosquito, Temperature, vector-borne, West Nile virus

Subject Categories

Biology

Abstract

West Nile virus (WNV) is the most common mosquito-borne disease in the contiguous U.S. WNV is a member of the Flaviviridae family which is group of single stranded positive sense RNA genome viruses. It is commonly vectored by Culex mosquitoes and is found in a transmission cycle between its amplifying hosts of birds. Incidental hosts of WNV include people and animals. WNV is known to cause flu-like illness and in rare cases can become neuroinvasive. There are currently no approved therapeutics on the market for WNV. Since the beginning of the 20th century the earth’s average temperature has increased by 1°C. Ectothermic organisms, such as mosquitoes, are uniquely susceptible to such increases. Increases in temperature are known to alter mosquito life history traits, viral replication, and vector competence, all of which play a role in WNV transmission. The influence of temperature on West Nile virus transmission is multifaceted. Unique interactions among mosquito population, mosquito life history traits, viral evolution, and virus strain are key in determining temperature-dependent WNV transmission. In order to gain a better understanding of the relationship between temperature and transmission, unique WNV strains and Culex pipiens populations were utilized for experimental infection and passage studies under distinct thermal conditions. To gain a better understanding of the population specific effects of temperature and WNV transmission, field acquired Culex pipiens populations from upstate and downstate New York (NY) were utilized. Life history traits were recorded from egg hatch to death at geographically relevant and future predicted temperature. These data were then used to generate thermal performance curves and calculate the relative basic reproduction number (R0) of WNV. Results indicated differences in peak transmission temperature between upstate and downstate Cx. pipiens, demonstrating the importance of thermal sensitivity on a population level when predicting temperature-dependent vector-borne disease risk. To probe the influence of temperature on WNV evolution and adaptation serial passage of WNV at 25°C and 30°C was performed. Growth kinetics of pass 1 and pass 12 viruses were performed to measure replicative fitness and virus passage at 30°C was found to have increased replicative fitness at 25°C and 30°C, demonstrating broad adaptation. Additionally, passaging virus at 30°C resulted in an increased number of amino acid changes. These data suggest WNV has the ability to adapt to increasing temperature. Rising temperatures could drive diversification and emergence of high fitness strains in nature, which is likely to result in increased transmission. WNV was first identified in New York State (NYS) in 1999. Given that temperature has increased in NYS it was hypothesized that contemporary WNV may have increased fitness at higher temperatures compared to historic WNV strains. Here Cx. pipiens vector competence of eight WNV strains was measured at 20°, 24°C, and 28°C. Cx. pipiens were found to have increased vector competence for contemporary strains across temperature. Utilizing previously published mosquito life history trait data, vectorial capacity (VC) was calculated. Contemporary strains were found to have increased VC at 20°C, 24°C, and 28°C. These results are consistent with temperature facilitating adaptation in nature and highlight the importance of strain specific differences of WNV risk under climate change. Current R0 calculations utilize adult life history traits from non-infectious studies, excluding the measurements of vector competence and extrinsic incubation period. Here, the role of infection status in WNV transmission was investigated by performing a modified transmission assay where lifespan, host feeding rate, and fecundity were compared among unexposed and WNV exposed Cx. pipiens. Strain-specific differences were additionally compared using representative WN02 genotype and NY10 genotype strains. Results demonstrate reduced VC of WN02 and NY10 disseminated mosquitoes from 20°C - 30°C compared to that of unexposed mosquitoes. These data demonstrate the importance of considering infection status when modeling WNV risk across temperature. Together, these studies outline the complex influence of temperature on WNV transmission, demonstrating the importance of unique vector-virus interactions in temperature-dependent vector-borne disease risk. These data can be utilized to refine WNV R0 predictions under climate change in order to inform public health interventions for the prevention of WNV transmission.

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