Projects
Assessing the impact of diet on susceptibility to dengue virus infection
Although dengue is endemic in Africa, cases of severe dengue are rare. The sub-Saharan rural African diet is high in complex carbohydrates and low in refined sugars and fats. On the other hand, the Western diet, high in refined sugar and fat is associated with high levels of cytokines and resultant pro-inflammatory phenotype. We hypothesize that consuming the African diet, high in complex carbohydrates and low in fat, modifies the DENV translatome in a manner that reduces replication and promotes cellular metabolism and immune responses that minimizes susceptibility to DENV infection. The outcomes of this study will allow us to fill crucial gaps in our knowledge of the intricacies surrounding the resilience to DENV infection and severe symptoms among the African populations and how we can harness this diet to improve outcomes in the US.
Assessment of Aedes aegypti molecular responses to genetically distinct Zika Virus strains
Interactions of arboviruses with fundamental cellular processes and arboviral suppression by mosquito immune defense mechanisms form the molecular basis of how the mosquito vector controls infection by the arbovirus.We hypothesize that the Neotropics ZIKV strains has evolved to suppress the mosquito immune response resulting in an enhanced viral replication and a suppression of the immune gene transcripts. The findings of our study will provide insights into host factors driving transmission dynamics in geographical clusters.
Identification of intrahost genetic mutants of global ZIKV strains
RNA viruses exhibit high mutation rates, resulting in mutant swarms. These mutations can lead to fitness gains or losses and are often neutral. Our study is aimed at identifying mutant swarms associated with the different Zika virus (ZIKV) lineages and studying the effect of the mutant swarm on ZIKV replicative fitness, transmission efficiency, and disease severity. The findings of our study will provide insights into the disparities in transmission efficiency by Aedes aegypti populations caused by ZIKV mutants.
Aedes aegypti saliva microbiome as a predictive tool for dengue severity
Arthropod midgut microbiota is also present in their saliva and can be egested at the skin bite site leading to dual colonization of the vertebrate host with pathogens and saliva microbiome. Our past findings have observed a richer microbial community in the saliva of Aedes aegypti compared to their midgut, yet some of the taxa were common in Aedes aegypti midgut and saliva. We hypothesize that a correlation exist between Aedes aegypti saliva microbiome presence, viral load and immune response to DENV infection and is informative of disease severity. The findings of our study will lead to an improved understanding of the initial stages of virus transmission and potential targets for transmission barrier development.
Delineating factors driving disparities in Crimean Congo Hemorrhagic Fever disease outbreaks in unique habitats of the East African pastoralist zones.
As a zoonotic infection, Crimean Congo Hemorrhagic Fever (CCHF) is a major public health concern throughout Africa. In East Africa, Uganda has experienced multiple independent CCHF outbreaks since 2013. In contrast, there has been no CCHFV outbreak and only one documented case of acute human CCHFV infection in Kenya. This in spite of the high prevalence of Hyalomma marginatum, the primary vector of CCHFV, in the intense pastoralist region of Northern Kenya and very low environmental suitability for Hyalomma spps in the CCHFV hostspot regions of Uganda. We aim to utilize an interdisciplinary approach to identify and characterize the transmission risk patterns of CCHFV in East Africa. These studies will fill knowledge gaps on the biological factors that shape the transmission of CCHF and other tick-borne pathogens in the East Africa regions experiencing increased tick-borne disease outbreaks and inform the development of innovative strategies for tick control globally.