Wolbachia-mosquito-arbovirus interactions and dengue transmission blocking in Aedes aegypti

 

Supervisor: Professor Steven Sinkins- School of Infection & Immunity 

 

Rotation project:

Wolbachia are intracellular, maternally inherited bacterial symbionts found in many insects.

The mosquito Aedes aegypti is naturally Wolbachia-free, but artificially introduced Wolbachia can completely block transmission of the viruses it transmits such as dengue and Zika.

Wolbachia also induce cytoplasmic incompatibility (CI), a sterility mechanism that allows it to rapidly invade insect populations. For these reasons Wolbachia are becoming important biocontrol of dengue.

A better understanding of the mechanistic basis of viral inhibition is needed in order to be able to deploy Wolbachia optimally for virus control.

Proteomic and functional assays comparing Wolbachia-carrying and Wolbachia-free Aedes aegypti cells have revealed that Wolbachia perturbs cholesterol and lipid transport in the cell, and this impacts viral replication.

The aims of the project will be to investigate how perturbations in lipid transport / homeostasis vary between Wolbachia strains and mosquito host species, and how their effects may differ between viruses.

We have already generated Aedes cell lines carrying a number of different Wolbachia strains, which reach different densities and show varying degrees of virus inhibition.

Various manipulations of regulatory genes will be carried out in these cell lines, the effects on lipids and Wolbachia density examined, and whether replication of dengue and Zika can be rescued.