ARBOVIRUS INFECTION DYNAMICS IN THE MOSQUITO AEDES AEGYPTI
Open Access
- Author:
- Novelo Canto, Mario
- Graduate Program:
- Entomology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 09, 2021
- Committee Members:
- Elizabeth Mcgraw, Chair & Dissertation Advisor
Jason Rasgon, Major Field Member
Gary Felton, Program Head/Chair
Margarita Lopez-Uribe, Outside Unit Member
David Kennedy, Outside Field Member - Keywords:
- DENV
CHIKV
dengue
chikungunya
mosquito
Aedes aegypti
infection dynamics
within-vector infection
EIP
intra-host
viral kinetics
co-infection
serotype
DENV-2
DENV-3
Wolbachia
TEP3
CECH
heritability
genetic correlation
mosquito immunity - Abstract:
- Arboviral diseases account for more than 17% of all infectious diseases globally, among the most prevalent are dengue fever and chikungunya, with over half of world’s population at risk of infection. Although mortality is generally low, the morbidity caused by these pathogens is associated with a substantial socioeconomic burden. Occasionally, infection with dengue virus (DENV) can lead to death due to dengue shock syndrome in all ages and chikungunya virus (CHIKV) infection can be severe for infants, with nearly half of infected newborns experiencing encephalopathy and multiple organ dysfunction. Both DENV and CHIKV are RNA viruses transmitted through the bite of the mosquito Aedes aegypti. Arboviral infection in the mosquito is a complex process, as the dynamics of infection can be influenced by the genetic variation of the virus altering the infection rates and transmission potential in mosquitoes. Competition between strains or serotypes can also affect viral population dynamics within the vector, thus modulating the transmission potential. This happens in nature when mosquitoes take multiple blood meals from several different hosts, each infected with a different or multiple virus. How different viruses interact and compete inside the mosquito during the stepwise process of infection or how the vector immune response changes in response to these different viruses is an area of vital research. Due to the lack of an effective vaccine and antiviral drugs, vector control is the most efficient strategy in reducing arbovirus transmission. Therefore, understanding the basic processes shaping vector-virus interactions is necessary for both implementation of more effective control strategies and the development of genetic modifications (GMO) and biocontrol in mosquitoes to limit transmission. Current example of such technologies includes clustered regularly interspaced short palindromic repeats (CRISPR) and the use of the endosymbiont Wolbachia. The three major aims of my dissertation are to investigate the 1) infection dynamics of DENV in the mosquito Ae. aegypti; 2) competitive interactions between co-infecting DENV serotypes in both wild type and Wolbachia – infected mosquitoes and 3) genetic basis of Ae. aegypti immune response to DENV and CHIKV infection. In chapter 1 1 I reviewed the history and role of Ae. aegypti as a disease vector and the importance of my research by studying the process of infection with different arboviruses inside the vector. In chapter 2 I examined the infection dynamics of DENV in the mosquito Ae. aegypti, specifically, the effect of infectious dose and serotype on the growth kinetics of virus in the tissues define the stepwise process of infection in the mosquito body. In chapter 3 I studied the competitive interactions between co-infecting DENV serotypes both in wild type mosquitoes and in Wolbachia-infected Ae. aegypti. Chapter 4 examines the comparative genetic basis of Ae. aegypti response to DENV and CHIKV infection using a family-breeding design. Finally, chapter 5 synthesizes the findings of the dissertation, including future directions, as well as discussing unanswered questions in this research area.