Arboviral Infection Dynamics and Evolutionary Genetics of Mosquito Vectors
Open Access
- Author:
- Henderson, Cory
- Graduate Program:
- Molecular, Cellular, and Integrative Biosciences
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- June 14, 2021
- Committee Members:
- Elizabeth Mcgraw, Chair of Committee
Jason Rasgon, Major Field Member & Dissertation Advisor
Melissa Rolls, Program Head/Chair
Isabella Cattadori, Major Field Member
Joyce Jose, Outside Unit & Field Member - Keywords:
- Mosquito
Virus
Mayaro
Zika
Anopheles
Aedes
Genomes
Transcriptomics
RNAi
siRNA
piRNA
Toll Pathway
Apoptosis - Abstract:
- Increasing globalization and climate change have contributed to increase and spread of arboviral pathogens. Mayaro virus (MAYV) is an arboviral pathogen in the genus Alphavirus that is circulating in South America with potential to spread to na ve regions. MAYV is also one of the few viruses with the ability to be transmitted by mosquitoes in the genus Anopheles, as well as the typical arboviral transmitting mosquitoes in the genus Aedes. Anopheles mosquitoes are the principal vectors for malaria and lymphatic filariasis, and they demonstrate limited evidence for arboviral transmission in laboratory and natural contexts. Vector management approaches require an understanding of the ecological, epidemiological, and biological context of the species in question. To address these aspects of vector management, I studied the interactions between co-circulating arboviral pathogens in vector mosquitoes, investigated the molecular basis for arboviral infection of vector species, and produced novel genome assemblies from understudied mosquito vector species. First, I describe co- and super-infection of Aedes aegypti with MAYV and Zika virus (ZIKV) to understand the interaction dynamics of these viral pathogens. Zika virus (ZIKV) is a Flavivirus primarily transmitted by Aedes mosquitoes and has emerged as a major arboviral public health concern due to its capacity to cross the placenta effecting developing fetus in pregnant women. Our results show a significant reduction in the infection rate of ZIKV during a co-infection of ZIKV and MAYV but no variation in the infection rate of MAYV. I also demonstrate an increase in the infection rate of MAYV when the mosquito was previously infected with Zika virus. This study highlights the dynamics of co- and super-infection and its role in arboviral infections and transmission also highlights the importance of considering these dynamics during risk assessment in epidemic areas. To investigate the response of anopheline mosquitoes to alphaviral infection at time points integral to transmission, I detail the transcriptomic and small RNA responses of An. stephensi to infection with MAYV via infectious bloodmeal at 2, 7, and 14 days post infection (dpi). 487 unique transcripts were significantly regulated, 79 putative novel miRNAs were identified, and an siRNA response is observed targeting the MAYV genome. Gene ontology analysis of transcripts regulated at each timepoint suggested activation of the Toll pathway at 7 dpi and repression of pathways related to autophagy and apoptosis at 14 dpi. These findings provide a basic understanding of the infection response of An. stephensi to MAYV and help to identify host factors which might be useful to target to inhibit viral replication in Anopheles mosquitoes. Finally, I present novel genome assemblies for An. crucians, An. freeborni, An. albimanus, and An. quadrimaculatus and examine the evolutionary relationship between these species. I create a phylogeny using the newly sequenced anopheline genomes and further identify 525 single copy orthologs demonstrating evidence for positive selection on at least one branch of the phylogeny. Gene ontology terms such as calcium ion signaling, histone binding, and protein acetylation identified as being biased in the set of selected genes. These novel genome sequences will be useful in developing our understanding of the diverse biological traits that drive vectorial capacity in anophelines